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Sample records for subchronic inhalation toxicology

  1. Inhalation toxicology of diesel fuel obscurant aerosol in Sprague-Dawley rats. Final report, Phase 3, subchronic exposures

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    Lock, S.; Dalbey, W.; Schmoyer, R.; Griesemer, R.

    1984-12-01

    Inhalation exposures were performed twice per week, for 13 weeks, to determine whether there was any potential toxicity to rats of comparatively low concentrations of a condensation aerosol from diesel fuel. Changes in breathing frequency and the response of animals to a loud sharp sound (startle response) were measured in selected animals prior to the start of the exposures, at various time points during the thirteen week exposure period, and at monthly intervals during the recovery period. Assays were performed on selected animals at the end of the exposure period, and again after the two month recovery period. Endpoints included pulmonary function tests, numbers of alveolar free cells, clinical chemistry, hematology, organ weights and histopathology. No mortalities were recorded during the exposure or recovery periods. Slight toxicity occurred at these low aerosol concentrations with the loss in body weight of all treated animals during the exposure period. During the exposure period there were also some slight changes in startle reflex, however, these were apparently acute effects, and there appeared to be no permanent CNS involvement as measured by this endpoint. Immediately post-exposure, the numbers of lavaged alveolar macrophages were slightly elevated in all aerosol exposed animals. Pulmonary function tests, pulmonary gas exchange and dynamic lung tests were all apparently unaffected by these low diesel fuel aerosol exposures. Changes in tissue weights in aerosol exposed animals were minor and the few histopathological lesions were randomly scattered amongst all groups included in this study and were more attributable to the age of the animals than any specific treatment group. No significant cumulative toxicity may be attributed to these diesel fuel aerosol exposures. 14 references, 1 figure, 42 tables.

  2. Subchronic inhalation toxicity of gold nanoparticles

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    Chung Yong

    2011-05-01

    Full Text Available Abstract Background Gold nanoparticles are widely used in consumer products, including cosmetics, food packaging, beverages, toothpaste, automobiles, and lubricants. With this increase in consumer products containing gold nanoparticles, the potential for worker exposure to gold nanoparticles will also increase. Only a few studies have produced data on the in vivo toxicology of gold nanoparticles, meaning that the absorption, distribution, metabolism, and excretion (ADME of gold nanoparticles remain unclear. Results The toxicity of gold nanoparticles was studied in Sprague Dawley rats by inhalation. Seven-week-old rats, weighing approximately 200 g (males and 145 g (females, were divided into 4 groups (10 rats in each group: fresh-air control, low-dose (2.36 × 104 particle/cm3, 0.04 μg/m3, middle-dose (2.36 × 105 particle/cm3, 0.38 μg/m3, and high-dose (1.85 × 106 particle/cm3, 20.02 μg/m3. The animals were exposed to gold nanoparticles (average diameter 4-5 nm for 6 hours/day, 5 days/week, for 90-days in a whole-body inhalation chamber. In addition to mortality and clinical observations, body weight, food consumption, and lung function were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for hematology and clinical chemistry tests, and organ weights were measured. Cellular differential counts and cytotoxicity measurements, such as albumin, lactate dehydrogenase (LDH, and total protein were also monitored in a cellular bronchoalveolar lavage (BAL fluid. Among lung function test measurements, tidal volume and minute volume showed a tendency to decrease comparing control and dose groups during the 90-days of exposure. Although no statistically significant differences were found in cellular differential counts, histopathologic examination showed minimal alveoli, an inflammatory infiltrate with a mixed cell type, and increased macrophages in the high-dose rats. Tissue

  3. Toxicological perspectives of inhaled therapeutics and nanoparticles.

    Science.gov (United States)

    Hayes, Amanda J; Bakand, Shahnaz

    2014-07-01

    The human respiratory system is an important route for the entry of inhaled therapeutics into the body to treat diseases. Inhaled materials may consist of gases, vapours, aerosols and particulates. In all cases, assessing the toxicological effect of inhaled therapeutics has many challenges. This article provides an overview of in vivo and in vitro models for testing the toxicity of inhaled therapeutics and nanoparticles implemented in drug delivery. Traditionally, inhalation toxicity has been performed on test animals to identify the median lethal concentration of airborne materials. Later maximum tolerable concentration denoted by LC0 has been introduced as a more ethically acceptable end point. More recently, in vitro methods have been developed, allowing the direct exposure of airborne material to cultured human target cells on permeable porous membranes at the air-liquid interface. Modifications of current inhalation therapies, new pulmonary medications for respiratory diseases and implementation of the respiratory tract for systemic drug delivery are providing new challenges when conducting well-designed inhalation toxicology studies. In particular, the area of nanoparticles and nanocarriers is of critical toxicological concern. There is a need to develop toxicological test models, which characterise the toxic response and cellular interaction between inhaled particles and the respiratory system.

  4. SUBCHRONIC TOXICITY OF INHALED TOLUENE IN RATS: IMMUNOLOGY, CARDIAC GENE EXPRESSION AND MARKERS OF OXIDATIVE STRESS.

    Science.gov (United States)

    The health effects of long-term exposure to volatile organic compounds (VOCs) are poorly understood, due primarily to insufficient human exposure data and inconsistent animal models. To develop a rodent model of long-term exposure to VOCs, a sub-chronic inhalation study with mult...

  5. Toxicological evaluation of subchronic use of pioglitazone in mice

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    Said Said Elshama

    2016-07-01

    Full Text Available Objective(s: Pioglitazone (Actos is one of the most controversial recent oral antidiabetic drugs. It was originally authorized in the European Union in 2000, and approved as an oral monotherapy for overweight second type of diabetic patients in 2002. It belongs to the thiazolidinedione group which some of its members have been withdrawn from the market due to the hepatotoxicity or cardiotoxicity effects.This studyinvestigates sub-chronic use of pioglitazone induced toxicity in mice by the assessment of renal and liver function tests, cardiac enzymes, and some hematological indices with histological changes of liver, kidney, heart, and bladder. Materials and Methods: 120 albino mice were divided into four groups; 30 in each. The first group (control received water, second (diabetic group received alloxan only, while the third and the fourth groups received alloxan with 200 and 400 mg/kg/day of pioglitazone, respectively for 90 days. Results: Prolonged use of pioglitazone induced significant abnormalities of hepatic, renal, and cardiac biomarkers and some hematological indices associated with histopathological changes in the liver, kidney, heart, and bladder that increased based on administered dose. Conclusion: Subchronic use of pioglitazone leads to hepatic, renal, cardiac, hematological, and bladder affection depending on the applied dose.

  6. Titanium dioxide: inhalation toxicology and epidemiology.

    Science.gov (United States)

    Hext, Paul M; Tomenson, John A; Thompson, Peter

    2005-08-01

    Titanium dioxide (TiO(2)) is manufactured worldwide in large quantities for use in a wide range of applications and is normally considered to be toxicologically inert. Findings of tumours in the lungs of rats exposed chronically to high concentrations of TiO(2), but not in similarly exposed mice or hamsters, suggest that the tumorigenic response may be a rat-specific phenomenon but nonetheless raises concerns for potential human health effects. With the limited toxicological understanding of species differences in response to inhaled TiO(2) and a similarly limited amount of epidemiological information with respect to TiO(2) exposure in the workplace, a consortium of TiO(2) manufacturers in Europe (under the European Chemistry Industry Council; CEFIC) and in North America (under the American Chemistry Council; ACC) initiated a programme of research to investigate inter-species differences as a result of exposure to TiO(2) and to conduct detailed epidemiological surveys of the major manufacturing sites. The toxicology studies exposed rats, mice and hamsters to pigment-grade TiO(2) (PG-TiO(2), 0, 10, 50 and 250 mg m(-3)) or ultrafine TiO(2) (UF-TiO(2), 0, 0.5, 2 and 10 mg m(-3)) for 90 days and the lung burdens and tissue responses were evaluated at the end of the exposure period and for up to 1 year after exposure. Results demonstrated clear species differences. Rats and mice had similar lung burdens and clearance rates while hamsters showed high clearance rates. At high lung particle burdens, rats showed a marked progression of histopathological lesions throughout the post-exposure period while mice and hamsters showed minimal initial lesions with recovery apparent during the post-exposure period. Lung neutrophil responses, a sensitive marker of inflammatory changes, reflected the development or recovery of the histopathological lesions. The use of surface area rather than gravimetric lung burden provided closer correlates of the burden to the biological effect

  7. Health Effects of Subchronic Inhalation of Simulated Downwind Coal Combustion Emissions

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    Joe Mauderly

    2009-01-07

    The purpose of this project was to conduct a comprehensive laboratory-based evaluation of selected respiratory and cardiac health hazards of subchronic (up to 6 months) inhalation of simulated key components of 'downwind plume' emissions of coal combustion. This project was performed as an integral part of a joint government-industry program termed the 'National Environmental Respiratory Center' (NERC), which is aimed at disentangling the roles of different physical-chemical air pollutants and their sources in the health effects associated statistically with air pollution. The characterization of the exposure atmosphere and the health assays were identical to those employed in the NERC protocols used to evaluate other pollution source emissions, such as diesel, gasoline, and wood combustion. The project had two phases, each encompassing multiple tasks. Guidelines for the composition of the exposure atmosphere were set by consensus of an expert workshop. Development of the capability to generate the exposure atmosphere and pilot studies of the comparative exposure composition using two coal types were accomplished in Phase 1. In Phase 2, the toxicological study was conducted using Powder River Basin Sub-bituminous coal. NETL provided 50% support for the work in Phase 1 and had intended to provide 20% support for the work in Phase 2. Phase 1 is completed and Phase 2 is in the final stages. All animal exposures were completed without incident, and the composition of the exposure atmospheres met the targets. All of the health sample collections are completed, but some samples remain to be analyzed. Data summaries and final statistical analysis of results remain to be completed. The goal is to submit all publications before the end of FY-08. Repeated exposure to simulated downwind coal emissions caused some significant health effects, but the number of effects tended to be fewer than those caused by the other NERC exposures (diesel and gasoline

  8. Inhalation Toxicology Research Institute annual report 1987-1988

    International Nuclear Information System (INIS)

    Mauderly, J.L.; Mewhinney, J.A.; Bechtold, W.E.; Sun, J.D.; Coons, T.A.

    1988-12-01

    The mission of the Inhalation Toxicology Research Institute is to investigate the magnitude of human health effects that result from the inhalation of airborne materials at home, in the work place, or in the general environment. Diseases of the respiratory tract are major causes of suffering and death, and many of these diseases are directly related to the materials that people breath. The Institute's research is directed toward obtaining a better understanding of the basic biology of the respiratory tract and the mechanisms by which inhaled materials produce respiratory disease. Special attention is focused on studying the airborne materials released by various energy technologies, as well as those associated with national defense activities. The research uses a wide-ranging, comprehensive array of investigative approaches that are directed toward characterizing the source of the airborne material, following the material through its potential transformation in the air, identifying the mechanisms that govern its inhalation and deposition in the respiratory tract, and determining the fate of these inhaled materials in the body and the health effects they produce. The ultimate objectives are to determine the roles played by inhaled materials in the development of disease processes adn to estimate the risk they pose by inhaled materials in the development of disease processes and to estimate the risk they pose to humans who may be exposed to them. This report contains brief research papers that reflect the scope and recent findings of the Institute's research funded by the U.S. Department of Energy, principally through the Office of Health and Environmental Research. The papers are divided into topical sections. The first section, Characterization of Airborne Materials and Generation of Experimental Exposure Atmospheres, reflects the Institute's capabilities for fundamental aerosol research and the application of that expertise to toxicological studies. The second

  9. Inhalation Toxicology Research Institute annual report 1987-1988

    Energy Technology Data Exchange (ETDEWEB)

    Mauderly, J L; Mewhinney, J A; Bechtold, W E; Sun, J D; Coons, T A [eds.

    1988-12-01

    The mission of the Inhalation Toxicology Research Institute is to investigate the magnitude of human health effects that result from the inhalation of airborne materials at home, in the work place, or in the general environment. Diseases of the respiratory tract are major causes of suffering and death, and many of these diseases are directly related to the materials that people breath. The Institute's research is directed toward obtaining a better understanding of the basic biology of the respiratory tract and the mechanisms by which inhaled materials produce respiratory disease. Special attention is focused on studying the airborne materials released by various energy technologies, as well as those associated with national defense activities. The research uses a wide-ranging, comprehensive array of investigative approaches that are directed toward characterizing the source of the airborne material, following the material through its potential transformation in the air, identifying the mechanisms that govern its inhalation and deposition in the respiratory tract, and determining the fate of these inhaled materials in the body and the health effects they produce. The ultimate objectives are to determine the roles played by inhaled materials in the development of disease processes adn to estimate the risk they pose by inhaled materials in the development of disease processes and to estimate the risk they pose to humans who may be exposed to them. This report contains brief research papers that reflect the scope and recent findings of the Institute's research funded by the U.S. Department of Energy, principally through the Office of Health and Environmental Research. The papers are divided into topical sections. The first section, Characterization of Airborne Materials and Generation of Experimental Exposure Atmospheres, reflects the Institute's capabilities for fundamental aerosol research and the application of that expertise to toxicological studies. The second

  10. Inhalation Toxicology Research Institute. Annual report, October 1, 1978-September 30, 1979

    International Nuclear Information System (INIS)

    Henderson, R.F.; Diel, J.H.; Martinez, B.S.

    1979-12-01

    Research information is given by the annual report from the Inhalation Toxicology Research Institute with abstracts for each of the 109 papers. Major sections of interest are nuclear energy toxicology, solar energy toxicology, diesel technology toxicology, coal technology toxicology, and conservation technology toxicology. Also included are seven appendices covering publications of technical reports and publications in open literature, abstracts publications in the open literature, seminars presented by visiting scientists and presentations before scientific meetings, organization of the Inhalation Toxicology Research Institute, and the status of experiments using beagle dogs

  11. The inhalation toxicology of p-aramid fibrils.

    Science.gov (United States)

    Donaldson, Ken

    2009-01-01

    The pandemic of lung disease caused by asbestos has cast suspicion on any industrial fibrous material that can become airborne in respirable form in workplaces, such that the respirable fibres might be inhaled. Fibre toxicology arose as a sub-specialty of particle toxicology to address the specialised nature of fibre effects and has evolved substantially in the last 25 years. It has yielded valuable information on the dosimetry, structure-activity relationships, and mechanism involved in toxicological effects of a range of fibrous materials, including asbestos, other naturally occurring fibrous materials, and synthetic vitreous fibres. A robust structure/activity paradigm has emerged from this research that highlights fibre length, thinness, and biopersistence as major factors in determining the pathogenicity of a fibre. p-Aramid is a manufactured fibre composed of synthetic polyamide (poly paraphenylene terephthalamide) manufactured on a commercial scale since 1970 by polymerisation and spinning steps. It is used as an advanced composite and in fabrics, body armour, friction materials, etc. Respirable fibrils of p-aramid can be released from the fibres during working and can become airborne. A considerable body of research has been carried out into the hazard posed by inhaled p-aramid fibrils, and this review considers this body of literature and summarises the state-of-the-science in the toxicology of p-aramid fibrils in the light of the existing overarching fibre toxicology paradigm. The peer-reviewed studies demonstrate that p-aramid fibrils can be long and thin but that the fibrils are not biopersistent. Residence in the milieu of the lungs leads to fibre shortening, allowing efficient and complete phagocytosis and effective clearance. Subsequently the p-aramid hazard is low, and this is confirmed in animal studies. The mechanism of shortening of p-aramid fibrils is not well-understood, but may involve the action of macrophages on the fibrils following

  12. Sub-chronic inhalation of high concentrations of manganese sulfate induces lower airway pathology in rhesus monkeys

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    Wong Brian A

    2005-10-01

    Full Text Available Abstract Background Neurotoxicity and pulmonary dysfunction are well-recognized problems associated with prolonged human exposure to high concentrations of airborne manganese. Surprisingly, histological characterization of pulmonary responses induced by manganese remains incomplete. The primary objective of this study was to characterize histologic changes in the monkey respiratory tract following manganese inhalation. Methods Subchronic (6 hr/day, 5 days/week inhalation exposure of young male rhesus monkeys to manganese sulfate was performed. One cohort of monkeys (n = 4–6 animals/exposure concentration was exposed to air or manganese sulfate at 0.06, 0.3, or 1.5 mg Mn/m3 for 65 exposure days. Another eight monkeys were exposed to manganese sulfate at 1.5 mg Mn/m3 for 65 exposure days and held for 45 or 90 days before evaluation. A second cohort (n = 4 monkeys per time point was exposed to manganese sulfate at 1.5 mg Mn/m3 and evaluated after 15 or 33 exposure days. Evaluations included measurement of lung manganese concentrations and evaluation of respiratory histologic changes. Tissue manganese concentrations were compared for the exposure and control groups by tests for homogeneity of variance, analysis of variance, followed by Dunnett's multiple comparison. Histopathological findings were evaluated using a Pearson's Chi-Square test. Results Animals exposed to manganese sulfate at ≥0.3 mg Mn/m3 for 65 days had increased lung manganese concentrations. Exposure to manganese sulfate at 1.5 mg Mn/m3 for ≥15 exposure days resulted in increased lung manganese concentrations, mild subacute bronchiolitis, alveolar duct inflammation, and proliferation of bronchus-associated lymphoid tissue. Bronchiolitis and alveolar duct inflammatory changes were absent 45 days post-exposure, suggesting that these lesions are reversible upon cessation of subchronic high-dose manganese exposure. Conclusion High-dose subchronic manganese sulfate inhalation is

  13. Inhalation Toxicology Research Institute. Annual report, October 1, 1992--September 30, 1993

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    Nikula, K.J.; Belinsky, S.A.; Bradley, P.L. [eds.

    1993-11-01

    This annual report for the Inhalation Toxicology Research Institute for 1992-1993 consists of 60 individual reports prepared separately by investigators describing progress in their own projects. Most papers are 2-5 pages long.

  14. Inhalation Toxicology Research Institute annual report, October 1, 1993--September 30, 1994

    International Nuclear Information System (INIS)

    Belinsky, S.A.; Hoover, M.D.; Bradley, P.L.

    1994-11-01

    This document from the Inhalation Toxicology Research Institute includes annual reports in the following general areas: (I) Aerosol Technology and Characterization of Airborne Materials; (II) Deposition, transport, and clearance of inhaled Toxicants; (III) Metabolism and Markers of Inhaled Toxicants; (IV) Carcinogenic Responses to Toxicants; (V) Mechanisms of carcinogenic response to Toxicants; (VI) Non carcinogenic responses to inhaled toxicants; (VII) Mechanisms of noncarcinogenic Responses to Inhaled Toxicants; (VIII) The application of Mathematical Modeling to Risk Estimates. 9 appendices are also included. Selected papers are indexed separately for inclusion in the Energy Science and Technology Database

  15. Inhalation Toxicology Research Institute annual report, October 1, 1993--September 30, 1994

    Energy Technology Data Exchange (ETDEWEB)

    Belinsky, S. A.; Hoover, M. D.; Bradley, P. L. [eds.

    1994-11-01

    This document from the Inhalation Toxicology Research Institute includes annual reports in the following general areas: (I) Aerosol Technology and Characterization of Airborne Materials; (II) Deposition, transport, and clearance of inhaled Toxicants; (III) Metabolism and Markers of Inhaled Toxicants; (IV) Carcinogenic Responses to Toxicants; (V) Mechanisms of carcinogenic response to Toxicants; (VI) Non carcinogenic responses to inhaled toxicants; (VII) Mechanisms of noncarcinogenic Responses to Inhaled Toxicants; (VIII) The application of Mathematical Modeling to Risk Estimates. 9 appendices are also included. Selected papers are indexed separately for inclusion in the Energy Science and Technology Database.

  16. Acute, subchronic, and developmental toxicological properties of lubricating oil base stocks.

    Science.gov (United States)

    Dalbey, Walden E; McKee, Richard H; Goyak, Katy Olsavsky; Biles, Robert W; Murray, Jay; White, Russell

    2014-01-01

    Lubricating oil base stocks (LOBs) are substances used in the manufacture of finished lubricants and greases. They are produced from residue remaining after atmospheric distillation of crude oil that is subsequently fractionated by vacuum distillation and additional refining steps. Initial LOB streams that have been produced by vacuum distillation but not further refined may contain polycyclic aromatic compounds (PACs) and may present carcinogenic hazards. In modern refineries, LOBs are further refined by multistep processes including solvent extraction and/or hydrogen treatment to reduce the levels of PACs and other undesirable constituents. Thus, mildly (insufficiently) refined LOBs are potentially more hazardous than more severely (sufficiently) refined LOBs. This article discusses the evaluation of LOBs using statistical models based on content of PACs; these models indicate that insufficiently refined LOBs (potentially carcinogenic LOBs) can also produce systemic and developmental effects with repeated dermal exposure. Experimental data were also obtained in ten 13-week dermal studies in rats, eight 4-week dermal studies in rabbits, and seven dermal developmental toxicity studies with sufficiently refined LOBs (noncarcinogenic and commonly marketed) in which no observed adverse effect levels for systemic toxicity and developmental toxicity were 1000 to 2000 mg/kg/d with dermal exposures, typically the highest dose tested. Results in both oral and inhalation developmental toxicity studies were similar. This absence of toxicologically relevant findings was consistent with lower PAC content of sufficiently refined LOBs. Based on data on reproductive organs with repeated dosing and parameters in developmental toxicity studies, sufficiently refined LOBs are likely to have little, if any, effect on reproductive parameters.

  17. Acute, subacute and subchronic toxicological studies of carissa carandas leaves (ethanol extract): a plant active against cardiovascular diseases

    International Nuclear Information System (INIS)

    Shamim, S.

    2014-01-01

    The Purpose of this research study was to examine the toxicological effects of aqueous: ethanol (1:1) extract of Carissa carandas leaves extracts in rats. Methodolgy: Acute toxicity studies were conducted to check the LD50 values in experimental animals. Autopsy after acute toxicity revealed that no gross changes were observed in organs like liver, spleen, heart and kidney among the animals of group N (control) and S (treated). The appearance of organs of Group S animals was comparable with that of Group N animals. Results: No signs of toxicity and mortality were observed in treated group after sub acute toxicity as compared to the control group. The histopathological studies after subchronic toxicity in doses of 1750 mg/kg (p.o.) and 5000 mg/kg (p.o) showed no toxic effects on organs like liver, heart, kidney and spleen. While chronic toxicity in dose 5000 mg/kg (p.o.) showed some histological changes. (author)

  18. Inhalation Toxicology Research Institute. Annual report, October 1, 1981-September 30, 1982

    International Nuclear Information System (INIS)

    Snipes, M.B.; Marshall, T.C.; Martinez, B.S.

    1982-12-01

    Studies are presented of the effect on man of airborne particulates and gaseous emissions associated with the production of energy. Included in the report from the Inhalation Toxicology Research Institute are papers on: (1) the physical and chemical characterization of energy technology aerosols; (2) laboratory studies of aerosol generation and characterization; (3) in vitro predictors of toxicity; (4) disposition and fate of inhaled materials; (5) dose-response relationships for inhaled radionuclides; (6) dose-response relationships for inhaled chemical toxicants; (7) biological factors which influence dose-response relationships; and (8) risk assessment

  19. Assessment of bioaccumulation, neuropathology, and neurobehavior following subchronic (90 days) inhalation in Sprague-Dawley rats exposed to manganese phosphate.

    Science.gov (United States)

    Normandin, Louise; Carrier, Gaétan; Gardiner, Phillip F; Kennedy, Greg; Hazell, Alan S; Mergler, Donna; Butterworth, Roger F; Philippe, Suzanne; Zayed, Joseph

    2002-09-01

    Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese (Mn) compound added to unleaded gasoline. It has been suggested that the combustion products of MMT containing Mn, such as manganese phosphate, could cause neurological symptoms similar to Parkinson's disease in humans. The aim of this work was to investigate the exposure-response relationship of bioaccumulation, neuropathology, and neurobehavior following a subchronic inhalation exposure to manganese phosphate in Sprague-Dawley male rats. Rats were exposed 6 h/day, 5 days/week for 13 consecutive weeks at 30, 300, or 3000 microg/m(3) Mn phosphate and compared to controls. Some rats were implanted with chronic EMG electrodes in the gastrocnemius muscle of the hind limb to assess tremor at the end of Mn exposure. Spontaneous motor activity was measured for 36 h using a computerized autotrack system. Rats were then sacrificed by exsanguination and Mn level in different brain tissues and other organs was determined by instrumental neutron activation analysis. Neuronal cell counts were obtained by assessing the sum of five grid areas for the caudate/putamen and the sum of two adjacent areas for the globus pallidus. Increased manganese concentrations were observed in all tissues of the brain and was dose-dependent in olfactory bulb and caudate/putamen. In fact, beginning with the highest level of exposure (3000 microg/m(3)) and ending with the control group, Mn concentrations in the olfactory bulb were 2.47 vs 1.28 vs 0.77 vs 0.64 ppm (P Locomotor activity assessment and tremor assessment did not reveal in neurobehavioral changes between the groups. Our results reinforce the hypothesis that the olfactory bulb and caudate/putamen are the main brain tissues for Mn accumulation after subchronic inhalation exposure.

  20. Impact of acute and subchronic inhalation exposure to PbO nanoparticles on mice

    Czech Academy of Sciences Publication Activity Database

    Lebedová, J.; Nováková, Z.; Večeřa, Zbyněk; Buchtová, Marcela; Dumková, J.; Dočekal, Bohumil; Bláhová, L.; Mikuška, Pavel; Míšek, Ivan; Hampl, A.; Hilscherová, K.

    (2018), s. 1-17 ISSN 1743-5390 R&D Projects: GA ČR(CZ) GBP503/12/G147; GA ČR(CZ) GAP503/11/2315 Institutional support: RVO:68081715 ; RVO:67985904 Keywords : nanoparticles * oxidative stress * subchronic * tissue damage Subject RIV: CB - Analytical Chemistry, Separation; DN - Health Impact of the Environment Quality (UZFG-Y) OBOR OECD: Analytical chemistry Impact factor: 6.428, year: 2016

  1. Evaluation of the Inhalation Toxicology Research Institute beagle dog closed breeding colony: a progress report

    International Nuclear Information System (INIS)

    Lustgarten, C.S.; Hobbs, C.H.; Muggenburg, B.A.; Benjamin, S.A.; Slauson, D.O.; Hahn, F.F.

    1974-01-01

    Since early 1968, a closed breeding colony has been in operation at the Inhalation Toxicology Research Institute to produce experimental dogs for inhalation toxicology studies and to replace colony breeding stock for producing dogs with a stable gene pool. From March 1, 1968 through July 15, 1974, 123 bitches were bred 613 times, resulting in 540 litters and 2809 puppies: a conception rate for this period of 88.9 percent. An average of 3.74 pups survived to one year of age. (U.S.)

  2. Inhalation Toxicology Research Institute annual report, October 1, 1982-September 30, 1983

    International Nuclear Information System (INIS)

    1983-12-01

    The mission of the Inhalation Toxicology Research Institute (ITRI) is to investigate the nature and magnitude of human health effects that might result from inhalation of airborne materials encountered in the work place, special attention is directed toward airborne particulate and gaseous emissions released by various energy technologies or from national defense activities. Included are five papers on the physical and chemical characterization of energy technology aerosols, 10 papers on laboratory studies of aerosol generation and characterization, 11 papers on in vitro predictors of toxicity, 12 papers on disposition and fate of inhaled materials, 24 papers on dose-response relationships for inhaled radionuclides, 3 papers on dose-response relationships for inhaled chemical toxicants, 8 papers on biological factors that influence dose-response relationships, and 4 papers are concerned with risk assessment

  3. IRIS Toxicological Review of Ammonia Noncancer Inhalation (Interagency Science Discussion Draft)

    Science.gov (United States)

    In September 2016, EPA finalized the IRIS assessment of Ammonia (Noncancer Inhalation). The Toxicological Review was reviewed internally by EPA and by other federal agencies and White House Offices before public release in June 2016. Consistent with the May 2009 IRIS assessment d...

  4. Inhalation toxicology of 241Am(NO3)3

    International Nuclear Information System (INIS)

    Ballou, J.E.; Gies, R.A.; Beasley, A.H.

    1980-01-01

    Inhaled 241 Am(NO 3 ) 3 was rapidly cleared from the lung (90% in 30 days) and translocated principally to skeleton. Although the estimated radiation dose to lung was twofold greater than the bone dose, the principal treatment-related lesion appeared to be osteosarcoma of the skeleton

  5. IRIS Toxicological Review of 1,4-Dioxane (with Inhalation ...

    Science.gov (United States)

    EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of 1,4-Dioxane (with inhalation update) that when finalized will appear on the Integrated Risk Information System (IRIS) database. 1,4-Dioxane is commonly used as a solvent, cleaning agent, chemical stabilizer, surface coating, adhesive agent, and an ingredient in chemical manufacture.

  6. Nanoparticles: a review of particle toxicology following inhalation exposure.

    Science.gov (United States)

    Bakand, Shahnaz; Hayes, Amanda; Dechsakulthorn, Finance

    2012-01-01

    It is expected that the rapid expansion of nanotechnology will bring many potential benefits. However, initial investigations have demonstrated that nanomaterials may adversely affect human health and the environment. By increasing the application of nanoparticles, protection of the human respiratory system from exposure to airborne nanoparticles and ultrafine particulates has become an emerging health concern. Available research has demonstrated an association between exposure to ambient airborne particulates and ultrafine particles and various adverse heath effects including increased morbidity and mortality. Nanomaterial structures are more likely to be toxic than the same materials of conventional sized samples and can be inhaled more deeply into the lungs. While the respiratory tract is considered as the primary target organ for inhaled nanoparticles, recent research has demonstrated that extrapulmonary organs are also affected. The very small size distribution and large surface area of nanoparticles available to undergo reactions may play a significant role in nanotoxicity, yet very little is known about their interactions with biological systems. This review explores the possible underlying toxicity mechanisms of nanoparticles following inhalational exposure. Nanoparticles differ from the same conventional material at a larger scale in physical, chemical and biological characteristics; therefore it is critical to recognize the potential risk of nanoparticle exposure using appropriate toxicity test methods. Current advances and limitations of toxicity assessment methods of nanoparticles are discussed highlighting the recent improvements of in vitro screening tools for the safety evaluation of the rapidly expanding area of nanotechnology.

  7. Inhalation Toxicology Research Institute annual report, October 1, 1994--September 30, 1995

    International Nuclear Information System (INIS)

    Bice, D.E.; Hahn, F.F.; Hoover, M.D.; Neft, R.E.; Thornton-Manning, J.R.; Bradley, P.L.

    1995-12-01

    The mission of the Inhalation Toxicology Research Institute (ITRI) is to conduct basic and applied research to improve the understanding of the nature and magnitude of the human health impacts of inhaling airborne materials in the home, workplace, and general environment. Institute research programs have a strong basic science orientation with emphasis on the nature and behavior of airborne materials, the fundamental biology of the respiratory tract, the fate of inhaled materials and the mechanisms by which they cause disease, and the means by which data produced in the laboratory can be used to estimate risks to human health. Disorders of the respiratory tract continue to be a major health concern, and inhaled toxicants are thought to contribute substantially to respiratory morbidity. As the largest laboratory dedicated to the study of basic inhalation toxicology, ITRI provides a national resource of specialized facilities, personnel, and educational activities serving the needs of government, academia, and industry. Selected papers are indexed separately for inclusion in the Energy Science and Technology Database

  8. Inhalation Toxicology Research Institute annual report, October 1, 1994--September 30, 1995

    Energy Technology Data Exchange (ETDEWEB)

    Bice, D.E.; Hahn, F.F.; Hoover, M.D.; Neft, R.E.; Thornton-Manning, J.R.; Bradley, P.L. [eds.

    1995-12-01

    The mission of the Inhalation Toxicology Research Institute (ITRI) is to conduct basic and applied research to improve the understanding of the nature and magnitude of the human health impacts of inhaling airborne materials in the home, workplace, and general environment. Institute research programs have a strong basic science orientation with emphasis on the nature and behavior of airborne materials, the fundamental biology of the respiratory tract, the fate of inhaled materials and the mechanisms by which they cause disease, and the means by which data produced in the laboratory can be used to estimate risks to human health. Disorders of the respiratory tract continue to be a major health concern, and inhaled toxicants are thought to contribute substantially to respiratory morbidity. As the largest laboratory dedicated to the study of basic inhalation toxicology, ITRI provides a national resource of specialized facilities, personnel, and educational activities serving the needs of government, academia, and industry. Selected papers are indexed separately for inclusion in the Energy Science and Technology Database.

  9. Toxicological evaluation of ethanolic extract from Stevia rebaudiana Bertoni leaves: Genotoxicity and subchronic oral toxicity.

    Science.gov (United States)

    Zhang, Qiannan; Yang, Hui; Li, Yongning; Liu, Haibo; Jia, Xudong

    2017-06-01

    Stevia rebaudiana Bertoni leaves have a long history of use as an abundant source of sweetener. The aqueous extract of stevia leaves and the predominant constitutes steviol glycosides have been intensively investigated. However, rare studies provided toxicological evaluation of bioactive components in the polar extract regarding their safety on human health. This study aimed to evaluate the toxicity of ethanolic extract of Stevia rebaudiana Bertoni leaves through a battery of in vitro and in vivo tests. Negative results were unanimously obtained from bacterial reverse mutation assay, mouse bone marrow micronucleus assay and mouse sperm malformation assay. Oral administration at dietary levels of 1.04%, 2.08% and 3.12% for 90 days did not induce significant behavioral, hematological, clinical, or histopathological changes in rats. Significant reduction of cholesterol, total protein and albumin was observed in female animals only at high dose level. The results demonstrated that Stevia rebaudiana Bertoni leaves ethanolic extract, which is rich in isochlorogenic acids, does not possess adverse effects through oral administration in this study. Our data provided supportive evidence for the safety of Stevia rebaudiana Bertoni leaves that may potentially be used in functional foods as well as nutritional supplements beyond sweetner. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Inhalation Toxicology Research Institute annual report, October 1, 1987--September 30, 1988

    Energy Technology Data Exchange (ETDEWEB)

    Mewhinney, J.A.; Bechtold, W.E.; Sun, J.D.; Coons, T.A. (eds.)

    1988-12-01

    The mission of the Inhalation Toxicology Research Institute is to investigate the nature and magnitude of human health effects that result from the inhalation of airborne materials at home, in the work place, or in the general environment. Diseases of the respiratory tract are major causes of suffering and death, and many of these diseases are directly related to the materials that people breathe. The Institute's research is directed toward obtaining a better understanding of the basic biology of the respiratory tract and the mechanisms by which inhaled materials produce respiratory disease. Special attention is focused on studying the airborne materials released by various energy technologies, as well as those associated with national defense activities. The research uses a wide-ranging, comprehensive array of investigative approaches that are directed toward characterizing the source of the airborne material, following the material through its potential transformation in the air, identifying the mechanisms that govern its inhalation and deposition in the respiratory tract, and determining the fate of these inhaled materials in the body and the health effects they produce. The ultimate objectives are to determine the roles played by inhaled materials in the development of disease processes and to estimate the risk they pose to humans who may be exposed to them.

  11. Toxicological Considerations, Toxicity Assessment, and Risk Management of Inhaled Nanoparticles.

    Science.gov (United States)

    Bakand, Shahnaz; Hayes, Amanda

    2016-06-14

    Novel engineered nanoparticles (NPs), nanomaterial (NM) products and composites, are continually emerging worldwide. Many potential benefits are expected from their commercial applications; however, these benefits should always be balanced against risks. Potential toxic effects of NM exposure have been highlighted, but, as there is a lack of understanding about potential interactions of nanomaterials (NMs) with biological systems, these side effects are often ignored. NPs are able to translocate to the bloodstream, cross body membrane barriers effectively, and affect organs and tissues at cellular and molecular levels. NPs may pass the blood-brain barrier (BBB) and gain access to the brain. The interactions of NPs with biological milieu and resulted toxic effects are significantly associated with their small size distribution, large surface area to mass ratio (SA/MR), and surface characteristics. NMs are able to cross tissue and cell membranes, enter into cellular compartments, and cause cellular injury as well as toxicity. The extremely large SA/MR of NPs is also available to undergo reactions. An increased surface area of the identical chemical will increase surface reactivity, adsorption properties, and potential toxicity. This review explores biological pathways of NPs, their toxic potential, and underlying mechanisms responsible for such toxic effects. The necessity of toxicological risk assessment to human health should be emphasised as an integral part of NM design and manufacture.

  12. Toxicological Considerations, Toxicity Assessment, and Risk Management of Inhaled Nanoparticles

    Directory of Open Access Journals (Sweden)

    Shahnaz Bakand

    2016-06-01

    Full Text Available Novel engineered nanoparticles (NPs, nanomaterial (NM products and composites, are continually emerging worldwide. Many potential benefits are expected from their commercial applications; however, these benefits should always be balanced against risks. Potential toxic effects of NM exposure have been highlighted, but, as there is a lack of understanding about potential interactions of nanomaterials (NMs with biological systems, these side effects are often ignored. NPs are able to translocate to the bloodstream, cross body membrane barriers effectively, and affect organs and tissues at cellular and molecular levels. NPs may pass the blood–brain barrier (BBB and gain access to the brain. The interactions of NPs with biological milieu and resulted toxic effects are significantly associated with their small size distribution, large surface area to mass ratio (SA/MR, and surface characteristics. NMs are able to cross tissue and cell membranes, enter into cellular compartments, and cause cellular injury as well as toxicity. The extremely large SA/MR of NPs is also available to undergo reactions. An increased surface area of the identical chemical will increase surface reactivity, adsorption properties, and potential toxicity. This review explores biological pathways of NPs, their toxic potential, and underlying mechanisms responsible for such toxic effects. The necessity of toxicological risk assessment to human health should be emphasised as an integral part of NM design and manufacture.

  13. Inhalation developmental toxicology studies: Gallium arsenide in mice and rats

    Energy Technology Data Exchange (ETDEWEB)

    Mast, T.J.; Greenspan, B.J.; Dill, J.A.; Stoney, K.H.; Evanoff, J.J.; Rommereim, R.L.

    1990-12-01

    Gallium arsenide is a crystalline compound used extensively in the semiconductor industry. Workers preparing solar cells and gallium arsenide ingots and wafers are potentially at risk from the inhalation of gallium arsenide dust. The potential for gallium arsenide to cause developmental toxicity was assessed in Sprague- Dawley rats and CD-1 (Swiss) mice exposed to 0, 10, 37, or 75 mg/m{sup 3} gallium arsenide, 6 h/day, 7 days/week. Each of the four treatment groups consisted of 10 virgin females (for comparison), and {approx}30 positively mated rats or {approx}24 positively mated mice. Mice were exposed on 4--17 days of gestation (dg), and rats on 4--19 dg. The day of plug or sperm detection was designated as 0 dg. Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice (rats, 20 dg; mice, 18 dg). Implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. Gallium and arsenic concentrations were determined in the maternal blood and uterine contents of the rats (3/group) at 7, 14, and 20 dg. 37 refs., 11 figs., 30 tabs.

  14. Health assessment of gasoline and fuel oxygenate vapors: subchronic inhalation toxicity.

    Science.gov (United States)

    Clark, Charles R; Schreiner, Ceinwen A; Parker, Craig M; Gray, Thomas M; Hoffman, Gary M

    2014-11-01

    Sprague Dawley rats were exposed via inhalation to vapor condensates of either gasoline or gasoline combined with various fuel oxygenates to assess whether their use in gasoline influences the hazard of evaporative emissions. Test substances included vapor condensates prepared from an EPA described "baseline gasoline" (BGVC), or gasoline combined with methyl tertiary butyl ether (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether (G/TAME), diisopropyl ether (G/DIPE), ethanol (G/EtOH), or t-butyl alcohol (G/TBA). Target concentrations were 0, 2000, 10,000 or 20,000mg/m(3) and exposures were for 6h/day, 5days/week for 13weeks. A portion of the animals were maintained for a four week recovery period to determine the reversibility of potential adverse effects. Increased kidney weight and light hydrocarbon nephropathy (LHN) were observed in treated male rats in all studies which were reversible or nearly reversible after 4weeks recovery. LHN is unique to male rats and is not relevant to human toxicity. The no observed effect level (NOAEL) in all studies was 10,000mg/m(3), except for G/MTBE (<2000) and G/TBA (2000). The results provide evidence that use of the studied oxygenates are unlikely to increase the hazard of evaporative emissions during refueling, compared to those from gasoline alone. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Inhalation Toxicology Research Institute. Annual report, October 1, 1995--September 30, 1996

    International Nuclear Information System (INIS)

    Bice, D.E.; Hahn, F.F.; Henderson, R.F.

    1996-12-01

    The Inhalation Toxicology Research Institute (ITRI) is a Government-owned facility leased and operated by the Lovelace Biomedical and Environmental Research Institute (LBERI) as a private, nonprofit research and testing laboratory. LBERI is an operating subsidiary of the Lovelace Respiratory Research Institute. Through September 30, 1996, ITRI was a Federally Funded Research and Development Center operated by Lovelace for the US Department of Energy (DOE) as a 'Single Program Laboratory' within the DOE Office of Health and Environmental Research, Office of Energy Research. Work for DOE continues in the privatized ITRI facility under a Cooperative Agreement. At the time of publication, approximately 70% of the Institute's research is funded by DOE, and the remainder is funded by a variety of Federal agency, trade association, individual industry, and university customers. The principal mission of ITRI is to conduct basic and applied research to improve our understanding of the nature and magnitude of the human health impacts of inhaling airborne materials in the home, workplace, and general environment. Institute research programs have a strong basic science orientation with emphasis on the nature and behavior of airborne materials, the fundamental biology of the respiratory tract, the fate of inhaled materials and the mechanisms by which they cause disease, and the means by which data produced in the laboratory can be used to estimate risks to human health. Disorders of the respiratory tract continue to be a major health concern, and inhaled toxicants are thought to contribute substantially to respiratory morbidity. As the country's largest facility dedicated to the study of basic inhalation toxicology, ITRI provides a national resource of specialized facilities, personnel, and educational activities serving the needs of government, academia, and industry

  16. Inhalation Toxicology Research Institute. Annual report, October 1, 1995--September 30, 1996

    Energy Technology Data Exchange (ETDEWEB)

    Bice, D.E.; Hahn, F.F.; Henderson, R.F. [eds.] [and others

    1996-12-01

    The Inhalation Toxicology Research Institute (ITRI) is a Government-owned facility leased and operated by the Lovelace Biomedical and Environmental Research Institute (LBERI) as a private, nonprofit research and testing laboratory. LBERI is an operating subsidiary of the Lovelace Respiratory Research Institute. Through September 30, 1996, ITRI was a Federally Funded Research and Development Center operated by Lovelace for the US Department of Energy (DOE) as a {open_quotes}Single Program Laboratory{close_quotes} within the DOE Office of Health and Environmental Research, Office of Energy Research. Work for DOE continues in the privatized ITRI facility under a Cooperative Agreement. At the time of publication, approximately 70% of the Institute`s research is funded by DOE, and the remainder is funded by a variety of Federal agency, trade association, individual industry, and university customers. The principal mission of ITRI is to conduct basic and applied research to improve our understanding of the nature and magnitude of the human health impacts of inhaling airborne materials in the home, workplace, and general environment. Institute research programs have a strong basic science orientation with emphasis on the nature and behavior of airborne materials, the fundamental biology of the respiratory tract, the fate of inhaled materials and the mechanisms by which they cause disease, and the means by which data produced in the laboratory can be used to estimate risks to human health. Disorders of the respiratory tract continue to be a major health concern, and inhaled toxicants are thought to contribute substantially to respiratory morbidity. As the country`s largest facility dedicated to the study of basic inhalation toxicology, ITRI provides a national resource of specialized facilities, personnel, and educational activities serving the needs of government, academia, and industry.

  17. Deposition, clearance, and shortening of Kevlar para-aramid fibrils in acute, subchronic, and chronic inhalation studies in rats.

    Science.gov (United States)

    Kelly, D P; Merriman, E A; Kennedy, G L; Lee, K P

    1993-10-01

    The deposition and clearance of lung-deposited Kevlar para-aramid fibrils (subfibers) have been investigated as part of a subchronic and chronic inhalation toxicity testing program. Fibrils recovered from lung tissue in para-aramid-exposed Sprague-Dawley rats were microscopically counted and measured after exposures to airborne fibrils which were about 12 microns median length (ML) and < 0.3 micron median diameter. In each of three studies lung-recovered fibrils were progressively shorter with increasing residence time in the lungs. Twenty-eight days after a single 6-hr exposure at 400 respirable fibrils per cubic centimeter (f/cm3) the ML of recovered fibrils decreased to about 5 microns. Twenty-four months after a 3-week exposure to 25 or 400 f/cm3, fibrils reached about 2 microns ML. After 2 years of continuous exposure at 2.5, 25, or 100 f/cm3 or 1 year exposure plus 1 year recovery at 400 f/cm3, fibril ML approached 4 microns. In the 2-year study, the lung-fiber accumulation rate/exposure concentration was similar for the three highest concentrations and was about 3 x greater than that seen at 2.5 f/cm3, indicating that concentrations of about 25 f/cm3 or more may overwhelm clearance mechanisms. Time required for fibrils to be reduced to < 5 microns in the lung was markedly less at lower exposure concentration and shorter exposure time. The primary shortening mechanism is proposed to be long fibril cutting by enzymatic attack at fibril defects. However, length-selective fibril deposition and clearance may contribute to shortening in the first few days after exposure. The enzymatic cutting hypothesis is supported by measured increases in numbers of short fibers following cessation of exposures, continued shortening of the fibril length distribution up to 2 years following exposure, and in vitro fibril shortening after 3 months in a proteolytic enzyme preparation. The conclusion is that para-aramid fibrils are less durable in the lungs of rats than expected from

  18. Transcriptional responses in the rat nasal epithelium following subchronic inhalation of naphthalene vapor

    International Nuclear Information System (INIS)

    Clewell, H.J.; Efremenko, A.; Campbell, J.L.; Dodd, D.E.; Thomas, R.S.

    2014-01-01

    , respectively. Using a published physiologically based pharmacokinetic (PBPK) model to estimate target tissue dose relevant to the proposed mode of action (total naphthalene metabolism per gram nasal tissue), the lowest transcriptional BMDLs from this analysis equate to human continuous naphthalene exposure at approximately 0.3 ppm. It is unlikely that significant effects of naphthalene or its metabolites will occur at exposures below this concentration. - Highlights: • We investigated mode of action for carcinogenicity of inhaled naphthalene in rats. • Gene expression changes were measured in rat nasal tissues after 90 day exposures. • Support a non-linear mode of action (oxidative stress, inflammation, and proliferation) • Suggest a dose-dependent transition in the mode of action between 1.0 and 10 ppm • Transcriptional benchmark doses could inform point of departure for risk assessment

  19. Transcriptional responses in the rat nasal epithelium following subchronic inhalation of naphthalene vapor

    Energy Technology Data Exchange (ETDEWEB)

    Clewell, H.J., E-mail: hclewell@thehamner.org; Efremenko, A.; Campbell, J.L.; Dodd, D.E.; Thomas, R.S.

    2014-10-01

    , respectively. Using a published physiologically based pharmacokinetic (PBPK) model to estimate target tissue dose relevant to the proposed mode of action (total naphthalene metabolism per gram nasal tissue), the lowest transcriptional BMDLs from this analysis equate to human continuous naphthalene exposure at approximately 0.3 ppm. It is unlikely that significant effects of naphthalene or its metabolites will occur at exposures below this concentration. - Highlights: • We investigated mode of action for carcinogenicity of inhaled naphthalene in rats. • Gene expression changes were measured in rat nasal tissues after 90 day exposures. • Support a non-linear mode of action (oxidative stress, inflammation, and proliferation) • Suggest a dose-dependent transition in the mode of action between 1.0 and 10 ppm • Transcriptional benchmark doses could inform point of departure for risk assessment.

  20. Haematological, biochemical and histopathological aspects of Hericium erinaceus ingestion in a rodent model: A sub-chronic toxicological assessment.

    Science.gov (United States)

    Lakshmanan, Hariprasath; Raman, Jegadeesh; David, Pamela; Wong, Kah-Hui; Naidu, Murali; Sabaratnam, Vikineswary

    2016-12-24

    Hericium erinaceus is a culinary-medicinal mushroom and has a long history of usage in traditional Chinese medicine as a tonic for stomach disorders, ulcers and gastrointestinal ailments. The present investigation was aimed to evaluate the potential toxic effects of the aqueous extract from the fruiting bodies of H. erinaceus in rats by a sub-chronic oral toxicity study. In this sub-chronic toxicity study, rats were orally administered with the aqueous extract of H. erinaceus (HEAE) at doses of 250, 500 and 1000mg/kg body weight (b.w.) for 90 days. Body weights were recorded on a weekly basis and general behavioural changes were observed. The blood samples were subjected to haematological, biochemical, serum electrolyte, and antioxidant enzyme estimations. The rats were sacrificed and organs were processed and examined for histopathological changes. No mortality or morbidity was observed in all the treated and control rats. The results showed that the oral administration of HEAE daily at three different doses for 90 days had no adverse effect on the general behaviour, body weight, haematology, clinical biochemistry, and relative organ weights. Histopathological examination at the end of the study showed normal architecture except for few non-treatment related histopathological changes observed in liver, heart and spleen. The results of this sub-chronic toxicity study provides evidence that oral administration of HEAE is safe up to 1000mg/kg and H. erinaceus consumption is relatively non-toxic. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Toxicological assessment of enzyme-treated asparagus extract in rat acute and subchronic oral toxicity studies and genotoxicity tests.

    Science.gov (United States)

    Ito, Tomohiro; Ono, Tomoko; Sato, Atsuya; Goto, Kazunori; Miura, Takehito; Wakame, Koji; Nishioka, Hiroshi; Maeda, Takahiro

    2014-03-01

    The safety of enzyme-treated asparagus extract (ETAS) developed as a novel anti-stress functional material was assessed in acute and subchronic studies and genotoxicity assays. In the acute oral dose toxicity study, all rats survived during the test period and ETAS did not influence clinical appearance, body weight gain and necropsy findings at a dosage of 2000mg/kg body weight. Thus, the 50% lethal dose (LD50) of ETAS was determined to be greater than 2000mg/kg. The 90-day subchronic study (500, 1000 and 2000mg/kg body weight, delivered by gavage) in rats reported no significant adverse effects in food consumption, body weight, mortality, urinalysis, hematology, biochemistry, necropsy, organ weight and histopathology. In the micronucleus test of mice, the incidence of micronuclei in ETAS-administered groups (500, 1000 and 2000mg/kg/day, injected twice) was equivalent to that of the negative control group, while the positive control group receiving mitomycin C showed a high incidence. The potential of ETAS to induce gene mutation was tested using four Salmonella typhimurium strains and Escherichia coli WP2uvrA. The test sample was not mutagenic to the test strains. These results support the safety of ETAS as food and dietary supplement. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Toxicological evaluation in silico and in vivo of secondary metabolites of Cissampelos sympodialis in Mus musculus mice following inhalation.

    Science.gov (United States)

    Alves, Mateus Feitosa; Ferreira, Larissa Adilis Maria Paiva; Gadelha, Francisco Allysson Assis Ferreira; Ferreira, Laércia Karla Diega Paiva; Felix, Mayara Barbalho; Scotti, Marcus Tullius; Scotti, Luciana; de Oliveira, Kardilândia Mendes; Dos Santos, Sócrates Golzio; Diniz, Margareth de Fátima Formiga Melo

    2017-12-04

    The ethanolic extract of the leaves of Cissampelos sympodialis showed great pharmacological potential, with inflammatory and immunomodulatory activities, however, it showed some toxicological effects. Therefore, this study aims to verify the toxicological potential of alkaloids of the genus Cissampelos through in silico methodologies, to develop a method in LC-MS/MS verifying the presence of alkaloids in the infusion and to evaluate the toxicity of the infusion of the leaves of C. sympodialis when inhaled by Swiss mice. Results in silico showed that alkaloid 93 presented high toxicological potential along with the products of its metabolism. LC-MS/MS results showed that the infusion of the leaves of this plant contained the alkaloids warifteine and methylwarifteine. Finally, the in vivo toxicological analysis of the C. sympodialis infusion showed results, both in biochemistry, organ weights and histological analysis, that the infusion of C. sympodialis leaves presents a low toxicity.

  3. Bioaccumulation and locomotor effects of manganese phosphate/sulfate mixture in Sprague-Dawley rats following subchronic (90 days) inhalation exposure

    International Nuclear Information System (INIS)

    Salehi, Fariba; Krewski, Daniel; Mergler, Donna; Normandin, Louise; Kennedy, Greg; Philippe, Suzanne; Zayed, Joseph

    2003-01-01

    Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese (Mn) compound added to unleaded gasoline in Canada. The primary combustion products of MMT are Mn phosphate, Mn sulfate, and a Mn phosphate/Mn sulfate mixture. Concerns have been raised that the combustion products of MMT containing Mn could be neurotoxic, even at low levels of exposure. The objective of this study is to investigate exposure-response relationships for bioaccumulation and locomotor effects following subchronic inhalation exposure to a mixture of manganese phosphates/sulfate mixture. A control group and three groups of 30 male Sprague-Dawley rats were exposed in inhalation chambers for a period of 13 weeks, 5 days per week, 6 h a day. Exposure concentrations were 3000, 300, and 30 μg/m 3 . At the end of the exposure period, locomotor activity and resting time tests were conducted for 36 h using a computerized autotrack system. Rats were then euthanized by exsanguination and Mn concentrations in different tissues (liver, lung, testis, and kidney) and blood and brain (caudate putamen, globus pallidus, olfactory bulb, frontal cortex, and cerebellum) were determined by neutron activation analysis. Increased manganese concentrations were observed in blood, kidney, lung, testis, and in all brain sections in the highest exposure group. Mn in the lung and in the olfactory bulb were dose dependent. Our data indicate that the olfactory bulb accumulated more Mn than other brain regions following inhalation exposure. Locomotor activity was increased at 3000 μg/m 3 , but no difference was observed in resting time among the exposed groups. At the end of the experiment, rats exposed to 300 and 3000 μg/m 3 exhibited significantly decreased body weight in comparison with the control group. Biochemical profiles also revealed some significant differences in certain parameters, specifically alkaline phospatase, urea, and chlorate

  4. Bioaccumulation and locomotor effects of manganese phosphate/sulfate mixture in Sprague-Dawley rats following subchronic (90 days) inhalation exposure.

    Science.gov (United States)

    Salehi, Fariba; Krewski, Daniel; Mergler, Donna; Normandin, Louise; Kennedy, Greg; Philippe, Suzanne; Zayed, Joseph

    2003-09-15

    Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese (Mn) compound added to unleaded gasoline in Canada. The primary combustion products of MMT are Mn phosphate, Mn sulfate, and a Mn phosphate/Mn sulfate mixture. Concerns have been raised that the combustion products of MMT containing Mn could be neurotoxic, even at low levels of exposure. The objective of this study is to investigate exposure-response relationships for bioaccumulation and locomotor effects following subchronic inhalation exposure to a mixture of manganese phosphates/sulfate mixture. A control group and three groups of 30 male Sprague-Dawley rats were exposed in inhalation chambers for a period of 13 weeks, 5 days per week, 6 h a day. Exposure concentrations were 3000, 300, and 30 microg/m(3). At the end of the exposure period, locomotor activity and resting time tests were conducted for 36 h using a computerized autotrack system. Rats were then euthanized by exsanguination and Mn concentrations in different tissues (liver, lung, testis, and kidney) and blood and brain (caudate putamen, globus pallidus, olfactory bulb, frontal cortex, and cerebellum) were determined by neutron activation analysis. Increased manganese concentrations were observed in blood, kidney, lung, testis, and in all brain sections in the highest exposure group. Mn in the lung and in the olfactory bulb were dose dependent. Our data indicate that the olfactory bulb accumulated more Mn than other brain regions following inhalation exposure. Locomotor activity was increased at 3000 microg/m(3), but no difference was observed in resting time among the exposed groups. At the end of the experiment, rats exposed to 300 and 3000 microg/m(3) exhibited significantly decreased body weight in comparison with the control group. Biochemical profiles also revealed some significant differences in certain parameters, specifically alkaline phospatase, urea, and chlorate.

  5. Sub-chronic inhalation of lead oxide nanoparticles revealed their broad distribution and tissue-specific subcellular localization in target organs

    Czech Academy of Sciences Publication Activity Database

    Dumková, J.; Smutná, Tereza; Vrlíková, Lucie; Le Coustumer, P.; Večeřa, Zbyněk; Dočekal, Bohumil; Mikuška, Pavel; Čapka, Lukáš; Fictum, P.; Hampl, A.; Buchtová, Marcela

    2017-01-01

    Roč. 14, č. 1 (2017), č. článku 55. ISSN 1743-8977 R&D Projects: GA ČR(CZ) GAP503/11/2315; GA ČR(CZ) GBP503/12/G147 Institutional support: RVO:67985904 ; RVO:68081715 Keywords : nanoparticles * lead oxide * electron microscopy * toxicity * inhalation Subject RIV: FP - Other Medical Disciplines; CB - Analytical Chemistry, Separation (UIACH-O) OBOR OECD: Toxicology; Analytical chemistry (UIACH-O) Impact factor: 8.577, year: 2016

  6. Subchronic 13-week inhalation exposure of rats to multiwalled carbon nanotubes: toxic effects are determined by density of agglomerate structures, not fibrillar structures.

    Science.gov (United States)

    Pauluhn, Jürgen

    2010-01-01

    Wistar rats were nose-only exposed to multiwalled carbon nanotubes (MWCNT, Baytubes) in a subchronic 13-week inhalation study. The focus of study was on respiratory tract and systemic toxicity, including analysis of MWCNT biokinetics in the lungs and lung-associated lymph nodes (LALNs). The time course and concentration dependence of pulmonary effects were examined by bronchoalveolar lavage (BAL) and histopathology up to 6 months postexposure. Particular emphasis was directed to the comparative characterization of MWCNT structures prior to and after micronization and dry powder dispersion into inhalation chambers. These determinations were complemented by additional analyses in digested BAL cells. Animals were exposed on 6 h/day, 5 days per week for 13 consecutive weeks to 0, 0.1, 0.4, 1.5, and 6 mg/m(3). The subchronic exposure to respirable solid aerosols of MWCNT was tolerated without effects suggestive of systemic toxicity. Kinetic analyses demonstrated a markedly delayed clearance of MWCNT from lungs at overload conditions. Translocation into LALNs occurred at 1.5 and 6 mg/m(3) and required at least 13 weeks of study to become detectable. At these exposure levels, the lung and LALN weights were significantly increased. Sustained elevations in BAL polymorphonuclear neutrophils and soluble collagen occurred at these concentrations with borderline effects at 0.4 mg/m(3). Histopathology revealed principal exposure-related lesions at 0.4 mg/m(3) and above in the upper respiratory tract (goblet cell hyper- and/or metaplasia, eosinophilic globules, and focal turbinate remodeling) and the lower respiratory tract (inflammatory changes in the bronchioloalveolar region and increased interstitial collagen staining). Granulomatous changes and a time-dependent increase of a bronchioloalveolar hyperplasia occurred at 6 mg/m(3). All end points examined were unremarkable at 0.1 mg/m(3) (no-observed-adverse-effect-level). In summary, this study demonstrates that the induced

  7. Evaluation of the dose-response and fate in the lung and pleura of chrysotile-containing brake dust compared to chrysotile or crocidolite asbestos in a 28-day quantitative inhalation toxicology study.

    Science.gov (United States)

    Bernstein, D M; Toth, B; Rogers, R A; Sepulveda, R; Kunzendorf, P; Phillips, J I; Ernst, H

    2018-04-26

    This study provides an understanding of the biokinetics and potential toxicology in the lung and pleura following inhalation of brake-dust (brakes manufactured with chrysotile). The design included a 28-day repeated multi-dose inhalation exposure (6 h/d, 5 d/wk, 4 wks) followed by 28-days without exposure. Fiber control groups included a similar grade chrysotile as used in the brakes and a commercial crocidolite asbestos. Aerosol fiber distributions of the chrysotile and crocidolite were similar (fiber-length > 20 μm/cm 3 : Chrysotile-low/high 42/62; Crocidolite-low/high 36/55; WHO-fibers/cm 3 : Chrysotile-low/high 192/219; Crocidolite-low/high 211/255). The total number of aerosol particles/cm 3 in the brake-dust was similar to that in the chrysotile (Brake-dust 710-1065; Chrysotile 532-1442). Brake-dust at particle exposure levels equal to or greater than chrysotile or crocidolite caused no indication of microgranulomas, epithelial hyperplasia, or fibrosis (Wagner score brake-dust and chrysotile-HD groups or in thickness of visceral or parietal pleural. The crocidolite exposure resulted in extensive inflammatory response, collagen development and adhesions between the visceral and parietal surfaces with double the surface thickness. These results provide essential information for the design of a subsequent subchronic study. Copyright © 2018. Published by Elsevier Inc.

  8. Combustion-derived nanoparticles: A review of their toxicology following inhalation exposure

    Directory of Open Access Journals (Sweden)

    Mills Nicholas

    2005-10-01

    Full Text Available Abstract This review considers the molecular toxicology of combustion-derived nanoparticles (CDNP following inhalation exposure. CDNP originate from a number of sources and in this review we consider diesel soot, welding fume, carbon black and coal fly ash. A substantial literature demonstrates that these pose a hazard to the lungs through their potential to cause oxidative stress, inflammation and cancer; they also have the potential to redistribute to other organs following pulmonary deposition. These different CDNP show considerable heterogeneity in composition and solubility, meaning that oxidative stress may originate from different components depending on the particle under consideration. Key CDNP-associated properties of large surface area and the presence of metals and organics all have the potential to produce oxidative stress. CDNP may also exert genotoxic effects, depending on their composition. CDNP and their components also have the potential to translocate to the brain and also the blood, and thereby reach other targets such as the cardiovascular system, spleen and liver. CDNP therefore can be seen as a group of particulate toxins unified by a common mechanism of injury and properties of translocation which have the potential to mediate a range of adverse effects in the lungs and other organs and warrant further research.

  9. Comprehensive Baseline Environmental Audit of the Inhalation Toxicology Research Institute, Albuquerque, New Mexico

    International Nuclear Information System (INIS)

    1993-06-01

    This report documents the results of the Comprehensive Baseline Environmental Audit conducted at the Inhalation Toxicology Research Institute (ITRI) in Albuquerque, New Mexico. The scope of the audit at the ITRI was comprehensive, addressing environmental activities in the technical areas of air; soils, sediments, and biota; surface water/drinking water; groundwater; waste management; toxic and chemical materials; quality assurance; radiation; inactive waste sites; environmental management; and environmental monitoring programs. Specifically assessed was the compliance of ITRI operations and activities with Federal, state, and local regulations; DOE Orders; internal operating standards; and best management practices. Onsite activities included inspection of ITRI facilities and operations; review of site documents; interviews with DOE and contractor personnel, as well as representatives from state regulatory agencies; and reviews of previous appraisals. Using these sources of information, the environmental audit team developed findings, which fell into two general categories: compliance findings and best management practice findings. Each finding also identifies apparent causal factor(s) that contributed to the finding and will assist line management in developing ''root causes'' for implementing corrective actions

  10. Subchronic effects of inhaled ambient particulate matter on glucose homeostasis and target organ damage in a type 1 diabetic rat model

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Yuan-Horng [Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan (China); Department of Medical Research, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan (China); Charles, Chou C.-K. [Research Center for Environmental Changes, Academia Sinica, Taipei, Taiwan (China); Wang, Jyh-Seng [Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan (China); Tung, Chun-Liang [Department of Pathology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan (China); Li, Ya-Ru; Lo, Kai [Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan (China); Cheng, Tsun-Jen, E-mail: tcheng@ntu.edu.tw [Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan (China); Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan (China)

    2014-12-01

    Epidemiological studies have reported associations between particulate matter (PM) and cardiovascular effects, and diabetes mellitus (DM) patients might be susceptible to these effects. The chief chronic injuries resulting from DM are small vascular injuries (micro-vascular complications) or large blood vessel injuries (macro-vascular complications). However, toxicological data regarding the effects of PM on DM-related cardiovascular complications is limited. Our objective was to investigate whether subchronic PM exposure alters glucose homeostasis and causes cardiovascular complications in a type 1 DM rat model. We constructed a real world PM{sub 2.5} exposure system, the Taipei Air Pollution Exposure System for Health Effects (TAPES), to continuously deliver non-concentrated PM for subchronic exposure. A type 1 DM rat model was induced using streptozotocin. Between December 22, 2009 and April 9, 2010, DM rats were exposed to PM or to filtered air (FA) using TAPES in Taipei, Taiwan, 24 h/day, 7 days/week, for a total of 16 weeks. The average concentrations (mean [SD]) of PM{sub 2.5} in the exposure and control chambers of the TAPES were 13.30 [8.65] and 0.13 [0.05] μg/m{sup 3}, respectively. Glycated hemoglobin A1c (HbA1c) was significantly elevated after exposure to PM compared with exposure to FA (mean [SD], 7.7% [3.1%] vs. 4.7% [1.0%], P < 0.05). Interleukin 6 and fibrinogen levels were significantly increased after PM exposure. PM caused focal myocarditis, aortic medial thickness, advanced glomerulosclerosis, and accentuation of tubular damage of the kidney (tubular damage index: 1.76 [0.77] vs. 1.15 [0.36], P < 0.001). PM exposure might induce the macro- and micro-vascular complications in DM through chronic hyperglycemia and systemic inflammation. - Highlights: • The study demonstrated cardiovascular and renal effects of PM in a rat model of DM. • TAPES is a continuous, real world, long-term PM exposure system. • HbA1c, a marker of glycemic

  11. Subchronic effects of inhaled ambient particulate matter on glucose homeostasis and target organ damage in a type 1 diabetic rat model

    International Nuclear Information System (INIS)

    Yan, Yuan-Horng; Charles, Chou C.-K.; Wang, Jyh-Seng; Tung, Chun-Liang; Li, Ya-Ru; Lo, Kai; Cheng, Tsun-Jen

    2014-01-01

    Epidemiological studies have reported associations between particulate matter (PM) and cardiovascular effects, and diabetes mellitus (DM) patients might be susceptible to these effects. The chief chronic injuries resulting from DM are small vascular injuries (micro-vascular complications) or large blood vessel injuries (macro-vascular complications). However, toxicological data regarding the effects of PM on DM-related cardiovascular complications is limited. Our objective was to investigate whether subchronic PM exposure alters glucose homeostasis and causes cardiovascular complications in a type 1 DM rat model. We constructed a real world PM 2.5 exposure system, the Taipei Air Pollution Exposure System for Health Effects (TAPES), to continuously deliver non-concentrated PM for subchronic exposure. A type 1 DM rat model was induced using streptozotocin. Between December 22, 2009 and April 9, 2010, DM rats were exposed to PM or to filtered air (FA) using TAPES in Taipei, Taiwan, 24 h/day, 7 days/week, for a total of 16 weeks. The average concentrations (mean [SD]) of PM 2.5 in the exposure and control chambers of the TAPES were 13.30 [8.65] and 0.13 [0.05] μg/m 3 , respectively. Glycated hemoglobin A1c (HbA1c) was significantly elevated after exposure to PM compared with exposure to FA (mean [SD], 7.7% [3.1%] vs. 4.7% [1.0%], P < 0.05). Interleukin 6 and fibrinogen levels were significantly increased after PM exposure. PM caused focal myocarditis, aortic medial thickness, advanced glomerulosclerosis, and accentuation of tubular damage of the kidney (tubular damage index: 1.76 [0.77] vs. 1.15 [0.36], P < 0.001). PM exposure might induce the macro- and micro-vascular complications in DM through chronic hyperglycemia and systemic inflammation. - Highlights: • The study demonstrated cardiovascular and renal effects of PM in a rat model of DM. • TAPES is a continuous, real world, long-term PM exposure system. • HbA1c, a marker of glycemic homeostasis, was

  12. Subchronic inhalation of carbon tetrachloride alters the tissue retention of acutely inhaled plutonium-239 nitrate in F344 rats and syrian golden hamsters

    International Nuclear Information System (INIS)

    Benson, J.M.; Barr, E.B.; Lundgren, D.L.

    1995-01-01

    Carbon tetrachloride (CCl 4 ) has been used extensively in the nuclear weapons industry, so it is likely that nuclear plant workers have been exposed to both CCl 4 and plutonium compounds. Future exposures may occur during open-quotes cleanupclose quotes operations at weapons productions sites such as the Hanford, Washington, and Rocky Flats, Colorado, facilities. Inhalation of 20 and 100 ppm CCl 4 by hamsters reduces uptake of 239 Pu solubilized from lung, shunting the 239 Pu to the skeleton

  13. Inhalation developmental toxicology studies of 1,3-butadiene in the rat: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Hackett, P.L.; Sikov, M.R.; Mast, T.J.; Brown, M.G.; Buschbom, R.L.; Clark, M.L.; Decker, J.R.; Evanoff, J.J.; Rommereim, R.L.; Rowe, S.E.; Westerberg, R.B.

    1987-11-01

    Maternal toxicity, reproductive performance and developmental toxicology were evaluated in Sprague-Dawley-derived rats during and following 6 hours/day, whole-body, inhalation exposures to 0, 40, 200, and 1000 ppM of 1,3-butadiene. The female rats (Ns = 24 to 28), which had mated with unexposed males, were exposed to the chemical from 6 through 15 dg and sacrificed on 20 dg. Maternal animals were weighed prior to mating and on 0, 6, 11, 16 and 20 dg; the rats were observed for mortality, morbidity and signs of toxicity during exposure and examined for gross tissue abnormalities at necropsy. Live fetuses were weighed and subjected to external, visceral and skeletal examinations to detect growth retardation and morphologic anomalies. There were no significant differences among treatment groups in maternal body weights or extragestational weights of rats exposed to 1,3-butadiene concentrations of 40 or 200 ppM, but, in animals exposed to 1000 ppM, significantly depressed body weight gains were observed during the first 5 days of exposure and extragestational weight gains tended to be lower than control values. These results, and the absence of clinical signs of toxicity, were considered to indicate that there was no maternal toxicity at exposure levels of 200 ppM or lower. The percentage of pregnant animals and the number of litters with live fetuses were unaffected by treatment. Under the conditions of this exposure regimen, there was no evidence for a teratogenic response to 1,3-butadiene exposure.

  14. Subchronic inhalation of carbon tetrachloride alters the tissue retention of acutely inhaled plutonium-239 nitrate in F344 rats and syrian golden hamsters

    Energy Technology Data Exchange (ETDEWEB)

    Benson, J.M.; Barr, E.B.; Lundgren, D.L. [and others

    1995-12-01

    Carbon tetrachloride (CCl{sub 4}) has been used extensively in the nuclear weapons industry, so it is likely that nuclear plant workers have been exposed to both CCl{sub 4} and plutonium compounds. Future exposures may occur during {open_quotes}cleanup{close_quotes} operations at weapons productions sites such as the Hanford, Washington, and Rocky Flats, Colorado, facilities. Inhalation of 20 and 100 ppm CCl{sub 4} by hamsters reduces uptake of {sup 239}Pu solubilized from lung, shunting the {sup 239}Pu to the skeleton.

  15. Inhalation Toxicology Research Institute annual report, October 1, 1983-September 30, 1984

    International Nuclear Information System (INIS)

    Guilmette, R.A.; Medinsky, M.A.

    1984-12-01

    The report describes research in the following areas: (1) aerosol generation and characterization; (2) deposition and fate of inhaled materials; (3) dose-response relationships for inhaled radionuclides; (4) dose-response relationships for inhaled chemical toxicants; and (5) biological factors that influence dose-response relationships. Project descriptions have been individually entered into the date base

  16. Subchronic inhalation of soluble manganese induces expression of hypoxia-associated angiogenic genes in adult mouse lungs

    International Nuclear Information System (INIS)

    Bredow, Sebastian; Falgout, Melanie M.; March, Thomas H.; Yingling, Christin M.; Malkoski, Stephen P.; Aden, James; Bedrick, Edward J.; Lewis, Johnnye L.; Divine, Kevin K.

    2007-01-01

    Although the lung constitutes the major exposure route for airborne manganese (Mn), little is known about the potential pulmonary effects and the underlying molecular mechanisms. Transition metals can mimic a hypoxia-like response, activating the hypoxia inducible factor-1 (HIF-1) transcription factor family. Through binding to the hypoxia-response element (HRE), these factors regulate expression of many genes, including vascular endothelial growth factor (VEGF). Increases in VEGF, an important biomarker of angiogenesis, have been linked to respiratory diseases, including pulmonary hypertension. The objective of this study was to evaluate pulmonary hypoxia-associated angiogenic gene expression in response to exposure of soluble Mn(II) and to assess the genes' role as intermediaries of potential pulmonary Mn toxicity. In vitro, 0.25 mM Mn(II) altered morphology and slowed the growth of human pulmonary epithelial cell lines. Acute doses between 0.05 and 1 mM stimulated VEGF promoter activity up to 3.7-fold in transient transfection assays. Deletion of the HRE within the promoter had no effect on Mn(II)-induced VEGF expression but decreased cobalt [Co(II)]-induced activity 2-fold, suggesting that HIF-1 may not be involved in Mn(II)-induced VEGF gene transcription. Nose-only inhalation to 2 mg Mn(II)/m 3 for 5 days at 6 h/day produced no significant pulmonary inflammation but induced a 2-fold increase in pulmonary VEGF mRNA levels in adult mice and significantly altered expression of genes associated with murine angiogenesis. These findings suggest that even short-term exposures to soluble, occupationally relevant Mn(II) concentrations may alter pulmonary gene expression in pathways that ultimately could affect the lungs' susceptibility to respiratory disease

  17. Effects of subchronic inhalation exposure of rats to emissions from a diesel engine burning soybean oil-derived biodiesel fuel.

    Science.gov (United States)

    Finch, G L; Hobbs, C H; Blair, L F; Barr, E B; Hahn, F F; Jaramillo, R J; Kubatko, J E; March, T H; White, R K; Krone, J R; Ménache, M G; Nikula, K J; Mauderly, J L; Van Gerpen, J; Merceica, M D; Zielinska, B; Stankowski, L; Burling, K; Howell, S

    2002-10-01

    There is increasing interest in diesel fuels derived from plant oils or animal fats ("biodiesel"), but little information on the toxicity of biodiesel emissions other than bacterial mutagenicity. F344 rats were exposed by inhalation 6 h/day, 5 days/wk for 13 wk to 1 of 3 dilutions of emissions from a diesel engine burning 100% soybean oil-derived fuel, or to clean air as controls. Whole emissions were diluted to nominal NO(x) concentrations of 5, 25, or 50 ppm, corresponding to approximately 0.04, 0.2, and 0.5 mg particles/m(3), respectively. Biologically significant, exposure-related effects were limited to the lung, were greater in females than in males, and were observed primarily at the highest exposure level. There was a dose-related increase in the numbers of alveolar macrophages and the numbers of particles in the macrophages, as expected from repeated exposure, but no neutrophil response even at the highest exposure level. The macrophage response was reduced 28 days after cessation of the exposure. Among the high-level females, the group mean lung weight/body weight ratio was increased, and minimal, multifocal bronchiolar metaplasia of alveolar ducts was observed in 4 of 30 rats. Lung weights were not significantly increased, and metaplasia of the alveolar ducts was not observed in males. An increase in particle-laden macrophages was the only exposure-related finding in lungs at the intermediate and low levels, with fewer macrophages and fewer particles per macrophage at the low level. Alveolar histiocytosis was observed in a few rats in both exposed and control groups. There were statistically significant, but minor and not consistently exposure-related, differences in body weight, nonpulmonary organ weights, serum chemistry, and glial fibrillary acidic protein in the brain. There were no significant exposure-related effects on survival, clinical signs, feed consumption, ocular toxicity, hematology, neurohistology, micronuclei in bone marrow, sister

  18. Inhalants

    Science.gov (United States)

    ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

  19. Toxicological Assessments of Rats Exposed Prenatally to Inhaled Vapors of Gasoline and Gasoline-Ethanol Blends

    Science.gov (United States)

    The primary alternative to petroleum-based fuels is ethanol, which is blended with gasoline in the United States at concentrations up to 15% for most automobiles. Efforts to increase the amount of ethanol in gasoline have prompted concerns about the potential toxicity of inhaled ...

  20. Influence of experimental pulmonary emphysema on the toxicological effects from inhaled nitrogen dioxide and diesel exhaust

    International Nuclear Information System (INIS)

    Mauderly, J.L.; Bice, D.E.; Cheng, Y.S.; Gillett, N.A.; Henderson, R.F.; Pickrell, J.A.; Wolff, R.K.

    1989-01-01

    This project examined the influence of preexisting, experimentally induced pulmonary emphysema on the adverse health effects in rats of chronic inhalation exposure to either nitrogen dioxide or automotive diesel-engine exhaust. Previous reports indicated that humans with chronic lung disease were among those most severely affected by episodic exposures to high concentrations of airborne toxicants. There were no previous reports comparing the effects of chronic inhalation exposure to components of automotive emissions in emphysematous and normal animals. The hypothesis tested in this project was that rats with preexisting pulmonary emphysema were more susceptible than rats with normal lungs to the adverse effects of the toxicant exposures. Young adult rats were housed continuously in inhalation exposure chambers and exposed seven hours per day, five days per week, for 24 months to nitrogen dioxide at 9.5 parts per million (ppm)2, or to diesel exhaust at 3.5 mg soot/m3, or to clean air as control animals. These concentrations were selected to produce mild, but distinct, effects in rats with normal lungs. Pulmonary emphysema was induced in one-half of the rats by intratracheal instillation of the proteolytic enzyme elastase six weeks before the toxicant exposures began. Health effects were evaluated after 12, 18, and 24 months of exposure. The measurements included respiratory function, clearance of inhaled radiolabeled particles, pulmonary immune responses to instilled antigen, biochemistry and cytology of airway fluid, total lung collagen, histopathology, lung morphometry, and lung burdens of diesel soot. The significance of influences of emphysema and toxicant exposure, and interactions between influences of the two treatments, were evaluated by analysis of variance

  1. Inhalants

    Science.gov (United States)

    ... uses inhalants may be unable to learn new things or may have a hard time carrying on simple conversations. If the cerebral ... get drugs on the street, it is really hard to know what you get, Sometimes, ... put in, all sorts of things could happen. And other times, one might get ...

  2. Inhalation toxicology of industrial plutonium and uranium oxide aerosols II. Deposition, retention and dosimetry

    International Nuclear Information System (INIS)

    Stanley, J.A.; Eidson, A.F.; Mewhinney, J.A.; Mo, T.

    1978-01-01

    A series of studies has been initiated in which powdered fuel materials obtained at industrial sites have been aerosolized in the dry state for the inhalation exposure of Fischer-344 rats, Beagle dogs and Cynomolgus monkeys to evaluate the potential biological hazard of such accidents. The materials chosen for study were 750 deg. C heat-treated mixed PuO 2 and UO 2 obtained from a ball milling process and 1750 deg. C heat-treated (U,Pu)O 1.97 powder obtained from the centerless grinding of fuel pellets. Care was taken to insure that the regenerated aerosols used in animal inhalation exposures had similar particle size and size distribution characteristics to those measured during glove box sampling at the industrial plant. The deposition, retention, distribution and excretion of these materials are being studied, using serial sacrifice of animals at times from 4 hours to several years after inhalation exposure. Periodic excreta samples are collected on all animals. Biological samples are analyzed to yield data on Pu, Am and U content. Data from animals sacrificed up to one year will be presented. The retention of 239 Pu and 241 Am in the lung and their subsequent clearance and translocation to other tissues such as liver, skeleton and tracheobronchial lymph nodes will be discussed in relation to the influence of species and of the physical chemical properties of the exposure aerosol. (author)

  3. Inhalation Toxicology Research Institute annual report, October 1, 1991--September 30, 1992

    International Nuclear Information System (INIS)

    Finch, G.L.; Nikula, K.J.; Bradley, P.L.

    1992-12-01

    The mission of ITRI is to conduct basic and applied research to improve our understanding of the nature and magnitude of the human health impacts of inhaling airborne materials in the home, workplace, and general environment. Institute research programs have a strong basic science orientation with emphasis on the nature and behavior of airborne materials, the fundamental biology of the respiratory tract, the fate of inhaled materials and the mechanisms by which they cause disease, and the means by which data produced in the laboratory can be used to estimate risks to human health. The papers in this annual report are organized along topical lines, rather than by research program, so that research within specific disciplines is more readily identified. The papers include summaries of research funded by both DOE and non-DOE sources, to represent the full scope of Institute activities. One section consists of summaries of research on the effects of injected actinides, conducted for DOE at the University of Utah

  4. Inhalation developmental toxicology studies: Teratology study of tetrahydrofuran in mice and rats: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Mast, T.J.; Evanoff, J.J.; Stoney, K.H.; Westerberg, R.B.; Rommereim, R.L.; Weigel, R.J.

    1988-08-01

    Tetrahydrofuran (THF), a four-carbon cyclic ether, is widely used as an industrial solvent. Although it has been used in large quantities for many years, few long-term toxicology studies, and no reproductive or developmental studies, have been conducted on THF. This study addresses the potential for THF to cause developmental toxicity in rodents by exposing Sprague-Dawley rats and Swiss (CD-1) mice to 0, 600, 1800, or 5000 ppm tetrahydrofuran (THF) vapors, 6 h/day, 7 dy/wk. Each treatment group consisted of 10 virgin females (for comparison), and approx.33 positively mated rats or mice. Positively mated mice were exposed on days 6--17 of gestation (dg), and rats on 6--19 dg. The day of plug or sperm detection was designated as O dg. Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice (rats, 20 dg; mice, 18 dg). Implants were enumerated and their status recorded and live fetuses were examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. 27 refs., 6 figs., 23 tabs.

  5. Inhalation toxicology of industrial plutonium and uranium oxide aerosols I. Physical chemical characterization

    International Nuclear Information System (INIS)

    Eidson, A.F.; Mewhinney, J.A.

    1978-01-01

    In the fabrication of mixed plutonium and uranium oxide fuel, large quantities of dry powders are processed, causing dusty conditions in glove box enclosures. Inadvertent loss of glove box integrity or failure of air filter systems can lead to human inhalation exposure. Powdered samples and aerosol samples of these materials obtained during two fuel fabrication process steps have been obtained. A regimen of physical chemical tests of properties of these materials has been employed to identify physical chemical properties which may influence their biological behavior and dosimetry. Materials to be discussed are 750 deg. C heat-treated, mixed uranium and plutonium oxides obtained from the ball milling operation and 1750 deg. C heat-treated, mixed uranium and plutonium oxides obtained from the centerless grinding of fuel pellets. Results of x-ray diffraction studies have shown that the powder generated by the centerless grinding of fuel pellets is best described as a solid solution of UO x and PuO x consistent with its temperature history. In vitro dissolution studies of both mixed oxide materials indicate a generally similar dissolution rate for both materials. In one solvent, the material with the higher temperature history dissolves more rapidly. The x-ray diffraction and in vitro dissolution results as well as preliminary results of x-ray photoelectron spectroscopic analyses will be compared and the implications for the associated biological studies will be discussed. (author)

  6. Toxicological assessments of rats exposed prenatally to inhaled vapors of gasoline and gasoline-ethanol blends.

    Science.gov (United States)

    Bushnell, Philip J; Beasley, Tracey E; Evansky, Paul A; Martin, Sheppard A; McDaniel, Katherine L; Moser, Virginia C; Luebke, Robert W; Norwood, Joel; Copeland, Carey B; Kleindienst, Tadeusz E; Lonneman, William A; Rogers, John M

    2015-01-01

    The primary alternative to petroleum-based fuels is ethanol, which may be blended with gasoline in the United States at concentrations up to 15% for most automobiles. Efforts to increase the amount of ethanol in gasoline have prompted concerns about the potential toxicity of inhaled ethanol vapors from these fuels. The well-known sensitivity of the developing nervous and immune systems to ingested ethanol and the lack of information about the neurodevelopmental toxicity of ethanol-blended fuels prompted the present work. Pregnant Long-Evans rats were exposed for 6.5h/day on days 9-20 of gestation to clean air or vapors of gasoline containing no ethanol (E0) or gasoline blended with 15% ethanol (E15) or 85% ethanol (E85) at nominal concentrations of 3000, 6000, or 9000 ppm. Estimated maternal peak blood ethanol concentrations were less than 5mg/dL for all exposures. No overt toxicity in the dams was observed, although pregnant dams exposed to 9000 ppm of E0 or E85 gained more weight per gram of food consumed during the 12 days of exposure than did controls. Fuel vapors did not affect litter size or weight, or postnatal weight gain in the offspring. Tests of motor activity and a functional observational battery (FOB) administered to the offspring between post-natal day (PND) 27-29 and PND 56-63 revealed an increase in vertical activity counts in the 3000- and 9000-ppm groups in the E85 experiment on PND 63 and a few small changes in sensorimotor responses in the FOB that were not monotonically related to exposure concentration in any experiment. Neither cell-mediated nor humoral immunity were affected in a concentration-related manner by exposure to any of the vapors in 6-week-old male or female offspring. Systematic concentration-related differences in systolic blood pressure were not observed in rats tested at 3 and 6 months of age in any experiment. No systematic differences were observed in serum glucose or glycated hemoglobin A1c (a marker of long-term glucose

  7. Oxidative Stress as a Mechanism Involved in Kidney Damage After Subchronic Exposure to Vanadium Inhalation and Oral Sweetened Beverages in a Mouse Model.

    Science.gov (United States)

    Espinosa-Zurutuza, Maribel; González-Villalva, Adriana; Albarrán-Alonso, Juan Carlos; Colín-Barenque, Laura; Bizarro-Nevares, Patricia; Rojas-Lemus, Marcela; López-Valdéz, Nelly; Fortoul, Teresa I

    Kidney diseases have notably increased in the last few years. This is partially explained by the increase in metabolic syndrome, diabetes, and systemic blood hypertension. However, there is a segment of the population that has neither of the previous risk factors, yet suffers kidney damage. Exposure to atmospheric pollutants has been suggested as a possible risk factor. Air-suspended particles carry on their surface a variety of fuel combustion-related residues such as metals, and vanadium is one of these. Vanadium might produce oxidative stress resulting in the damage of some organs such as the kidney. Additionally, in countries like Mexico, the ingestion of sweetened beverages is a major issue; whether these beverages alone are responsible for direct kidney damage or whether their ingestion promotes the progression of an existing renal damage generates controversy. In this study, we report the combined effect of vanadium inhalation and sweetened beverages ingestion in a mouse model. Forty CD-1 male mice were distributed in 4 groups: control, vanadium inhalation, 30% sucrose in drinking water, and vanadium inhalation plus sucrose 30% in drinking water. Our results support that vanadium inhalation and the ingestion of 30% sucrose induce functional and histological kidney damage and an increase in oxidative stress biomarkers, which were higher in the combined effect of vanadium plus 30% sucrose. The results also support that the ingestion of 30% sucrose alone without hyperglycemia also produces kidney damage.

  8. Review of the Evidence from Epidemiology, Toxicology, and Lung Bioavailability on the Carcinogenicity of Inhaled Iron Oxide Particulates.

    Science.gov (United States)

    Pease, Camilla; Rücker, Thomas; Birk, Thomas

    2016-03-21

    Since the iron-age and throughout the industrial age, humans have been exposed to iron oxides. Here, we review the evidence from epidemiology, toxicology, and lung bioavailability as to whether iron oxides are likely to act as human lung carcinogens. Current evidence suggests that observed lung tumors in rats result from a generic particle overload effect and local inflammation that is rat-specific under the dosing conditions of intratracheal instillation. This mode of action therefore, is not relevant to human exposure. However, there are emerging differences seen in vitro, in cell uptake and cell bioavailability between "bulk" iron oxides and "nano" iron oxides. "Bulk" particulates, as defined here, are those where greater than 70% are >100 nm in diameter. Similarly, "nano" iron oxides are defined in this context as particulates where the majority, usually >95% for pure engineered forms of primary particulates (not agglomerates), fall in the range 1-100 nm in diameter. From the weight of scientific evidence, "bulk" iron oxides are not genotoxic/mutagenic. Recent evidence for "nano" iron oxide is conflicting regarding genotoxic potential, albeit genotoxicity was not observed in an in vivo acute oral dose study, and "nano" iron oxides are considered safe and are being investigated for biomedical uses; there is no specific in vivo genotoxicity study on "nano" iron oxides via inhalation. Some evidence is available that suggests, hypothetically due to the larger surface area of "nano" iron oxide particulates, that toxicity could be exerted via the generation of reactive oxygen species (ROS) in the cell. However, the potential for ROS generation as a basis for explaining rodent tumorigenicity is only apparent if free iron from intracellular "nano" scale iron oxide becomes bioavailable at significant levels inside the cell. This would not be expected from "bulk" iron oxide particulates. Furthermore, human epidemiological evidence from a number of studies suggests that

  9. Aerial radiological survey of the United States Department of Energy's Sandia National Laboratories and Inhalation Toxicology Research Institute, Albuquerque, New Mexico. Date of survey: April 1981

    International Nuclear Information System (INIS)

    Boyns, P.K.

    1982-05-01

    An aerial radiological survey of the Sandia National Laboratories (SNLA) and the Inhalation Toxicology Research Institute (ITRI) was carried out in April 1981 by EG and G, Inc. for the United States Department of Energy. The survey consisted of an airborne measurement of both natural and man-made gamma radiation from the terrain surface in and around the SNLA and ITRI site. These measurements allowed a determination of the surface terrestrial spatial distribution of isotope concentrations. Results are reported as exposure rates and man-made isopleths and are superimposed on 240 m/cm scale map of the area. Gamma ray energy spectra are also presented for the net man-made radioelements. Several areas of man-made activity were detected in the SNLA and ITRI survey. These areas were associated with normal operations at the SNLA, ITRI and Kirtland Air Force Base. The presence of 241 Am was not detected in any of the areas surveyed

  10. Acute and Sub-Chronic Toxicity Potential Effects of Alchornea ...

    African Journals Online (AJOL)

    The open field test showed that sub-chronic administration increased rearing behavior significantly at the dose of 250 mg/kg/28 days but had no effect on grooming. In conclusion, the ethanolic extract has no toxicological effect as observed on hematological, biochemical and histopathological parameters even at the ...

  11. A CHRONIC INHALATION STUDY OF METHYL BROMIDE TOXICITY IN B6C3F1 MICE. (FINAL REPORT TO THE NATIONAL TOXICOLOGY PROGRAM)

    Energy Technology Data Exchange (ETDEWEB)

    HABER, S.B.

    1987-06-26

    This report provides a detailed account of a two year chronic inhalation study of methyl bromide toxicity in B6C3Fl mice conducted for the National Toxicology Program. Mice were randomized into three dose groups (10, 33 and 100 ppm methyl bromide) and one control group (0 ppm) per sex and exposed 5 days/week, 6 hours/day, for a total of 103 weeks. Endpoints included body weight; clinical signs and mortality, and at 6, 15 and 24 months of exposure, animals were sacrificed for organ weights, hematology and histopathology. In addition, a subgroup of animals in each dosage group was monitored for neurobehavioral and neuropathological changes. After only 20 weeks of exposure, 48% of the males and 12% of the females in the 100 ppm group had died. Exposures were terminated in that group and the surviving mice were observed for the duration of the study. Exposure of B6C3Fl mice to methyl bromide, even for only 20 weeks, produced significant changes in growth rate, mortality, organ weights and neurobehavioral functioning. These changes occurred in both males and females, but were more pronounced in males.

  12. Toxicological responses in SW mice exposed to inhaled pyrolysates of polymer/tobacco mixtures and blended tobacco.

    Science.gov (United States)

    Werley, Michael S; Lee, K Monika; Lemus-Olalde, Ranulfo

    2009-12-01

    Modern cigarette manufacturing is highly automated and produces millions of cigarettes per day. The potential for small inclusions of non-cigarette materials such as wood, cardboard packaging, plastic, and other materials exists as a result of bulk handling and high-speed processing of tobacco. Many non-tobacco inclusions such as wood, paper, and cardboard would be expected to yield similar pyrolysis products as a burning cigarette. The aircraft industry has developed an extensive literature on the pyrolysis products of plastics, however, that have been reported to yield toxic by-products upon burning, by-products that have been lethal in animals and humans upon acute exposure under some exposure conditions. Some of these smoke constituents have also been reported in cigarette smoke. Five synthetic polymers, nylon 6, acrylonitrile-butadiene-styrene (ABS), nylon 12, nylon 6,6, and acrylonitrile-butadiene (AB), and the natural polymer wool were evaluated by adding them to tobacco at a 3, 10, and 30% inclusion level and then pyrolyzing the mixture. The validated smoke generation and exposure system have been described previously. We used the DIN 53-436 tube furnace and nose-only exposure chamber in combination to conduct exposures in Swiss-Webster mice. Potentially useful biological endpoints for predicting hazards in humans included sensory irritation and pulmonary irritation, respiratory function, clinical signs, body weights, bronchoalveolar lavage (BAL) fluid analysis, carboxyhemoglogin, blood cyanide concentrations, and histopathology of the respiratory tract. Chemical analysis of selected smoke constituents in the test atmosphere was also performed in order to compare the toxicological responses with exposure to the test atmospheres. Under the conditions of these studies, biological responses considered relevant and useful for prediction of effects in humans were found for sensory irritation, body weights, BAL fluid analysis, and histopathology of the nose

  13. NTP Toxicology and Carcinogenesis Studies of Molybdenum Trioxide (CAS No. 1313-27-5) in F344 Rats and B6C3F1 Mice (Inhalation Studies).

    Science.gov (United States)

    1997-04-01

    Molybdenum is an essential element for the function of nitrogenase in plants and as a cofactor for enzymes including xanthine oxidoreductase, aldehyde oxidase, and sulfide oxidase in animals. Molybdenum trioxide is used primarily as an additive to steel and corrosion-resistant alloys. It is also used as a chemical intermediate for molybdenum products; an industrial catalyst; a pigment; a crop nutrient; components of glass, ceramics, and enamels; a flame retardant for polyester and polyvinyl chloride resins; and a reagent in chemical analyses. Molybdenum trioxide was nominated by the NCI for toxicity and carcinogenicity studies as a representative inorganic molybdenum compound. The production of molybdenum trioxide is the largest of all the molybdenum compounds examined. Male and female F344/N rats and B6C3F1 mice were exposed to molybdenum trioxide (approximately 99% pure) by inhalation for 14 days, 13 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and cultured Chinese hamster ovary cells. 14-DAY STUDY IN RATS: Groups of five male and five female F344/N rats were exposed to 0, 3, 10, 30, 100, or 300 mg molybdenum trioxide/m(3). Rats were exposed for 6 hours per day, 5 days per week, for a total of 10 exposure days during a 14-day period. All rats survived to the end of the study. The final mean body weights of male rats exposed to 100 mg/m(3) and male and female rats exposed to 300 mg/m(3) were significantly lower than those of the control groups. Male rats exposed to 300 mg/m(3) lost weight during the study. There were no clinical findings related to exposure to molybdenum trioxide. No chemical-related lesions were observed. 14-DAY STUDY IN MICE: Groups of five male and five female B6C3F1 mice were exposed to 0, 3, 10, 30, 100, or 300 mg molybdenum trioxide/m(3). Mice were exposed 6 hours per day, 5 days per week, for a total of 10 exposure days during a 14-day period. All mice survived to the end of the study. Final mean

  14. Toxicology and Carcinogenesis Studies of Furfuryl Alcohol (CAS No. 98-00-0) in F344/N Rats and B6C3F1 Mice (Inhalation Studies).

    Science.gov (United States)

    1999-02-01

    Furfuryl alcohol-based resins are used as binding agents in foundry sand and as corrosion inhibitors in mortar, grout, and cement. Because of their heat resistance, furan resins are used in the manufacture of fiberglass-reinforced plastic equipment. Furfuryl alcohol was selected for evaluation because of the absence of data on its carcinogenic potential and its large production volume, widespread use in manufacturing, and ubiquitous presence in consumer goods. Male and female F344/N rats and B6C3F1 mice were exposed to furfuryl alcohol (greater than 98% pure) by inhalation for 16 days, 14 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and mouse bone marrow cells. 16-DAY STUDY IN RATS: Groups of five male and five female rats were exposed to concentrations of 0, 16, 31, 63, 125, or 250 ppm furfuryl alcohol by inhalation, 6 hours per day, 5 days per week for 16 days. All male and female rats exposed to 250 ppm died by day 2 of the study, and one male rat exposed to 125 ppm died on day 5. Final mean body weights of male and female rats exposed to 125 ppm were significantly less than those of the chamber control groups. Male rats exposed to 31, 63, or 125 ppm and female rats exposed to 125 ppm gained less weight than the chamber control groups. Clinical findings included dyspnea, hypoactivity, and nasal and ocular discharge in males and females exposed to 63, 125, or 250 ppm. All exposed animals developed lesions in the nasal respiratory epithelium and olfactory epithelium, and the severities of these lesions generally increased with increasing exposure concentration. 16-DAY STUDY IN MICE: Groups of five male and five female mice were exposed to concentrations of 0, 16, 31, 63, 125, or 250 ppm furfuryl alcohol by inhalation, 6 hours per day, 5 days per week for 16 days. All male and female mice exposed to 250 ppm died by day 4 of the study, and one female mouse exposed to 125 ppm died on day

  15. NTP Toxicology and Carcinogenesis Studies of Chloroprene (CAS No. 126-99-8) in F344/N Rats and B6C3F1 Mice (Inhalation Studies).

    Science.gov (United States)

    1998-09-01

    Chloroprene is used almost exclusively in the manufacture of neoprene (polychloroprene). Chloroprene was chosen for study because it is a high-volume production chemical with limited information on its carcinogenic potential and because it is the 2-chloro analogue of 1,3-butadiene, a potent, multi-species, multi-organ carcinogen. Male and female F344/N rats and B6C3F1 mice were exposed to chloroprene (greater than 96% pure) by inhalation for 16 days, 13 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, Drosophila melanogaster, and B6C3F1 mice (bone marrow cells and peripheral blood erythrocytes). 16-Day Study in Rats: Groups of 10 male and 10 female F344/N rats were exposed to 0, 32, 80, 200, or 500 ppm chloroprene by inhalation, 6 hours per day, 5 days per week, for 16 days. Three 500 ppm males died on day 2 or 3 of the study. Mean body weight gains of 200 ppm males and females and 500 ppm females were significantly less than those of the chamber control groups. On the first day of exposure, rats exposed to 500 ppm were hypoactive and unsteady and had rapid shallow breathing. These effects were also observed to some degree in animals exposed to 200 ppm. After the second day of exposure, the effects in these groups worsened, and hemorrhage from the nose was observed. A normocytic, normochromic, responsive anemia; thrombocytopenia; and increases in serum activities of alanine aminotransferase, glutamate dehydrogenase, and sorbitol dehydrogenase occurred on day 4 in 200 ppm females and 500 ppm males. Kidney weights of 80 and 500 ppm females were significantly greater than those of the chamber control group, as were the liver weights of 200 and 500 ppm females. The incidences of minimal to mild olfactory epithelial degeneration of the nose in all exposed groups of males and females were significantly greater than those in the chamber control groups. The incidence of squamous metaplasia of the respiratory epithelium was

  16. Toxicology and carcinogenesis studies of tetralin (CAS No. 119-64-2) in F344/N rats and B6C3F1 mice (inhalation studies).

    Science.gov (United States)

    2011-04-01

    Tetralin is used as an industrial solvent primarily for naphthalene, fats, resins, oils, and waxes; as a solvent and stabilizer for shoe polishes and floor waxes; as a solvent for pesticides, rubber, asphalt, and aromatic hydrocarbons (e.g., anthracene); as a dye solvent carrier in the textile industry; as a substitute for turpentine in lacquers, paints, and varnishes; in paint thinners and as a paint remover; in alkali-resistant lacquers for cleaning printing ink from rollers and type; as a constituent of motor fuels and lubricants; for the removal of naphthalene in gas distribution systems; and as an insecticide for clothes moths. Tetralin was nominated by the National Cancer Institute for carcinogenicity and disposition studies because of its structure, high production volume, and high potential for worker and consumer exposure. Male and female F344/N rats and B6C3F1 mice were exposed to tetralin (at least 97% pure) by inhalation for 2 weeks, 3 months, or 2 years; male NCI Black Reiter (NBR) rats were exposed to tetralin by inhalation for 2 weeks. Male NBR rats do not produce 2u-globulin; the NBR rats were included to study the relationship of 2u-globulin and renal lesion induction. Genetic toxicology studies were conducted in Salmonella typhimurium, Escherichia coli, and mouse peripheral blood erythrocytes. 2-WEEK STUDY IN RATS: Groups of five male (F344/N and NBR) and five female (F344/N) rats were exposed to tetralin at air concentrations of 0, 7.5, 15, 30, 60, or 120 ppm, 6 hours plus T90 (12 minutes) per day, 5 days per week for 12 exposures. All rats survived to the end of the studies. The final mean body weight of female rats exposed to 120 ppm and mean body weight gains of female rats exposed to 30 ppm or greater were significantly less than those of the chamber controls. Final mean body weights of exposed groups of male NBR rats and mean body weight gains of all exposed groups of male rats were significantly less than those of the chamber controls. Dark

  17. Pulmonary toxicology of respirable particles. [Lead abstract

    Energy Technology Data Exchange (ETDEWEB)

    Sanders, C.L.; Cross, F.T.; Dagle, G.E.; Mahaffey, J.A. (eds.)

    1980-09-01

    Separate abstracts were prepared for the 44 papers presented in these proceedings. The last paper (Stannard) in the proceedings is an historical review of the field of inhalation toxicology and is not included in the analytics. (DS)

  18. Lack of micronucleus induction activity of ethyl tertiary-butyl ether in the bone marrow of F344 rats by sub-chronic drinking-water treatment, inhalation exposure, or acute intraperitoneal injection.

    Science.gov (United States)

    Noguchi, Tadashi; Kamigaito, Tomoyuki; Katagiri, Taku; Kondou, Hitomi; Yamazaki, Kazunori; Aiso, Shigetoshi; Nishizawa, Tomoshi; Nagano, Kasuke; Fukushima, Shoji

    2013-01-01

    Ethyl tertiary-butyl ether (ETBE) is an oxygenated gasoline additive synthesized from ethanol and isobutene that is used to reduce CO2 emissions. To support the Kyoto Protocol, the production of ETBE has undergone a marked increase. Previous reports have indicated that exposure to ETBE or methyl tertiary-butyl ether resulted in liver and kidney tumors in rats and/or mice. These reports raise concern about the effects of human exposure being brought about by the increased use of ETBE. The present study was conducted to evaluate the genotoxicity of ETBE using micronucleus induction of polychromatic erythrocytes in the bone marrow of male and female rats treated with ETBE in the drinking-water at concentrations of 0, 1,600, 4,000 or 10,000 ppm or exposed to ETBE vapor at 0, 500, 1,500 or 5,000 ppm for 13 weeks. There were no significant increases in micronucleus induction in either the drinking water-administered or inhalation-administered groups at any concentration of ETBE; although, in both groups red blood cells and hemoglobin concentration were slightly reduced in the peripheral blood in rats administered the highest concentration of ETBE. In addition, two consecutive daily intraperitoneal injections of ETBE at doses of 0, 250, 500 or 1,000 mg/kg did not increase the frequency of micronucleated bone marrow cells in either sex; all rats receiving intraperitoneal injections of ETBE at a dose of 2,000 mg/kg died after treatment day 1. These data suggest that ETBE is not genotoxic in vivo.

  19. Operational Toxicology Research

    Science.gov (United States)

    2006-08-01

    techniques for perchlorate in water, groundwater, soil and biological matrices such as blood, urine, milk . thyroid and other tissues required for...toxicity when they are inhaled or ingested and they are irritating to the skin and mucus membranes (Committee on Toxicology, 1996). When compared to...the data collected. Develop analytical techniques for perchlorate in water, groundwater, soil, and biological matrices such as blood, urine, milk

  20. Toxicological evaluation of the aqueous extract of Allium sativum ...

    African Journals Online (AJOL)

    The possible toxicological risks of Allium sativum aqueous extract upon consumption were assessed in mice and rats using acute and sub-chronic treatments. 36 male Swiss albino mice were used, and the various doses administered were 0, 2, 4, 8, 16 and 32 g/kg body weight. Mice were observed for behavioural changes ...

  1. Inhaled Steroids

    Science.gov (United States)

    ... considerations when your dosage changes. What about side effects and inhaled steroids? The most common side effects with inhaled steroids ... inhaled steroid has much less potential for side effects than steroid pills or syrups. There have been concerns regarding ...

  2. Inhalant Abuse

    Science.gov (United States)

    ... is when you pour the product into a bag, hold it over your mouth and nose, and inhale. How is inhalant abuse diagnosed? If you think your child is abusing inhalants, talk to them. Be honest and open. Tell them ...

  3. Pulmonary toxicology of respirable particles

    International Nuclear Information System (INIS)

    Sanders, C.L.; Cross, F.T.; Dagle, G.E.; Mahaffey, J.A.

    1980-09-01

    Separate abstracts were prepared for the 44 papers presented in these proceedings that deal will radioactive particles. The last paper (Stannard) in the proceedings is an historical review of the field of inhalation toxicology and is not included in the analytics

  4. Toxicology screen

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003578.htm Toxicology screen To use the sharing features on this page, please enable JavaScript. A toxicology screen refers to various tests that determine the ...

  5. Toxicology elements

    International Nuclear Information System (INIS)

    Viala, A.

    1998-01-01

    This work studies the different aspects of the modern toxicology: toxico-kinetic, biological, medico legal, food, professional, pharmaceuticals, environmental, social and regulatory. It is divided in three parts that consider the principle problems of general toxicology and analytical toxicology. (N.C.)

  6. Screening strategy to avoid toxicological hazards of inhaled nanoparticles for drug delivery: The use of a-quartz and nano zinc oxide particles as benchmark

    Energy Technology Data Exchange (ETDEWEB)

    Beyerle, Andrea; Schulz, Holger; Stoeger, Tobias [Institute of Inhalation Biology, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), Ingolstaedter Landstrasse 1, D - 85764 Neuherberg (Germany); Kissel, Thomas, E-mail: tobias.stoeger@helmholtz-muenchen.d [Department of Pharmaceutical Technology and Biopharmacy, Philipps- University Marburg (Germany)

    2009-02-01

    Nanotechnology is a broad, revolutionary field with promising advantages for new medicine. In this context the rapid development and improvement of so called nanocarriers is of high pharmaceutical interest and some devices are already on the market. In our project we aim to develop well characterized nanoscaled drug delivery systems for an inhalative application. To this end, we focus on the most adverse side-effects within the lung, the cytotoxic and the proinflammatory responses to these nanoparticles (NPs). Before performing any animal experiments, we start with an in vitro screening for analyzing the cytotoxic and proinflammatory effects of the investigated particles on two murine lung target cell lines, the alveolar epithelial like typ II cell line (LA4) and the alveolar macrophage cell line (MH-S). Three different endpoints were estimated, (i) cellular metabolic activity, determined by the WST-1 assay, (ii) membrane integrity, by detection of LDH release and hemolytic activity, and (iii) secretion of inflammatory mediators. To analyze the relative particle toxicity we choose two reference particles as benchmarks, (i) fine a-quartz, and (ii) ultrafine ZnO particles. The investigation of dose-response and kinetics of proinflammatory and toxic effects caused to the named cell lines provide an insight to a close evaluation of our cell based screening strategy. oc-quartz is well known for its inflammatory and toxic potential caused by inhalation, and nanosized ZnO particles - used in a broad field of nanotechnology like electronics, but also cosmetics and pharmaceuticals - is to a high degree cytotoxic and proinflammatory in vitro. Preliminary experiments indicated not only particle and cell specific inflammatory responses, but also different susceptibilities of the cell types being exposed to our benchmark particles regarding their size and surface activities. Exposure to the mum-sized a-quartz particles affected the viability of epithelia cells less than that of

  7. Screening strategy to avoid toxicological hazards of inhaled nanoparticles for drug delivery: The use of a-quartz and nano zinc oxide particles as benchmark

    Science.gov (United States)

    Beyerle, Andrea; Schulz, Holger; Kissel, Thomas; Stoeger, Tobias

    2009-02-01

    Nanotechnology is a broad, revolutionary field with promising advantages for new medicine. In this context the rapid development and improvement of so called nanocarriers is of high pharmaceutical interest and some devices are already on the market. In our project we aim to develop well characterized nanoscaled drug delivery systems for an inhalative application. To this end, we focus on the most adverse side-effects within the lung, the cytotoxic and the proinflammatory responses to these nanoparticles (NPs). Before performing any animal experiments, we start with an in vitro screening for analyzing the cytotoxic and proinflammatory effects of the investigated particles on two murine lung target cell lines, the alveolar epithelial like typ II cell line (LA4) and the alveolar macrophage cell line (MH-S). Three different endpoints were estimated, (i) cellular metabolic activity, determined by the WST-1 assay, (ii) membrane integrity, by detection of LDH release and hemolytic activity, and (iii) secretion of inflammatory mediators. To analyze the relative particle toxicity we choose two reference particles as benchmarks, (i) fine a-quartz, and (ii) ultrafine ZnO particles. The investigation of dose-response and kinetics of proinflammatory and toxic effects caused to the named cell lines provide an insight to a close evaluation of our cell based screening strategy. oc-quartz is well known for its inflammatory and toxic potential caused by inhalation, and nanosized ZnO particles - used in a broad field of nanotechnology like electronics, but also cosmetics and pharmaceuticals - is to a high degree cytotoxic and proinflammatory in vitro. Preliminary experiments indicated not only particle and cell specific inflammatory responses, but also different susceptibilities of the cell types being exposed to our benchmark particles regarding their size and surface activities. Exposure to the μm-sized a-quartz particles affected the viability of epithelia cells less than that of

  8. Screening strategy to avoid toxicological hazards of inhaled nanoparticles for drug delivery: The use of a-quartz and nano zinc oxide particles as benchmark

    International Nuclear Information System (INIS)

    Beyerle, Andrea; Schulz, Holger; Stoeger, Tobias; Kissel, Thomas

    2009-01-01

    Nanotechnology is a broad, revolutionary field with promising advantages for new medicine. In this context the rapid development and improvement of so called nanocarriers is of high pharmaceutical interest and some devices are already on the market. In our project we aim to develop well characterized nanoscaled drug delivery systems for an inhalative application. To this end, we focus on the most adverse side-effects within the lung, the cytotoxic and the proinflammatory responses to these nanoparticles (NPs). Before performing any animal experiments, we start with an in vitro screening for analyzing the cytotoxic and proinflammatory effects of the investigated particles on two murine lung target cell lines, the alveolar epithelial like typ II cell line (LA4) and the alveolar macrophage cell line (MH-S). Three different endpoints were estimated, (i) cellular metabolic activity, determined by the WST-1 assay, (ii) membrane integrity, by detection of LDH release and hemolytic activity, and (iii) secretion of inflammatory mediators. To analyze the relative particle toxicity we choose two reference particles as benchmarks, (i) fine a-quartz, and (ii) ultrafine ZnO particles. The investigation of dose-response and kinetics of proinflammatory and toxic effects caused to the named cell lines provide an insight to a close evaluation of our cell based screening strategy. oc-quartz is well known for its inflammatory and toxic potential caused by inhalation, and nanosized ZnO particles - used in a broad field of nanotechnology like electronics, but also cosmetics and pharmaceuticals - is to a high degree cytotoxic and proinflammatory in vitro. Preliminary experiments indicated not only particle and cell specific inflammatory responses, but also different susceptibilities of the cell types being exposed to our benchmark particles regarding their size and surface activities. Exposure to the μm-sized a-quartz particles affected the viability of epithelia cells less than that of

  9. Subchronic toxicological study of two artemisinin derivatives in dogs.

    Directory of Open Access Journals (Sweden)

    Ji-ye Yin

    Full Text Available The objective of our study was to profile and compare the systematic changes between orally administered artesunate and intramuscularly injected artemether at a low dose over a 3-month period (92 consecutive days in dogs. Intramuscular administration of 6 mg kg-1 artemether induced a decreased red blood cell (RBC count (anemia, concurrent extramedullary hematopoiesis in the spleen and inhibition of erythropoiesis in the bone marrow. We also observed a prolonged QT interval and neuropathic changes in the central nervous system, which demonstrated the cortex and motor neuron vulnerability, but no behavioral changes. Following treatment with artesunate, we observed a decreased heart rate, which was most likely due to cardiac conduction system damage, as well as a deceased RBC count, extramedullary hematopoiesis in the spleen and inhibition of erythropoiesis in the bone marrow. However, in contrast to treatment with artemether, neurotoxicity was not observed following treatment with artesunate. In addition, ultra-structural examination by transmission electron microscopy showed mitochondrial damage following treatment with artesunate. These findings demonstrated the spectrum of toxic changes that result upon treatment with artesunate and artemether and show that the prolonged administration of low doses of these derivatives result in diverse toxicity profiles.

  10. Sub-chronic toxicological studies of transition metal complexes of ...

    African Journals Online (AJOL)

    Md. Sharif Hasan

    2017-01-18

    Jan 18, 2017 ... naproxen showed more side effects than metal complexes which ..... Fosslein E. Adverse effects of nonsteroidal anti-inflammatory drugs on the ... association increases the anti-inflammatory and analgesic activity of ibuprofen.

  11. Sub-chronic toxicological studies of transition metal complexes of ...

    African Journals Online (AJOL)

    However, Naproxen metal complexes showed comparatively lower side effects than naproxen. Hematological report suggested that naproxen was in process of initiating inflammation which was justified by decreasing the mean value hemoglobin and hematocrit level and increasing the white blood cells level. There were ...

  12. Health effects of subchronic inhalation exposure to gasoline engine exhaust.

    Science.gov (United States)

    Reed, M D; Barrett, E G; Campen, M J; Divine, K K; Gigliotti, A P; McDonald, J D; Seagrave, J C; Mauderly, J L; Seilkop, S K; Swenberg, J A

    2008-10-01

    Gasoline engine emissions are a ubiquitous source of exposure to complex mixtures of particulate matter (PM) and non-PM pollutants; yet their health hazards have received little study in comparison with those of diesel emissions. As a component of the National Environmental Respiratory Center (NERC) multipollutant research program, F344 and SHR rats and A/J, C57BL/6, and BALBc mice were exposed 6 h/day, 7 days/week for 1 week to 6 months to exhaust from 1996 General Motors 4.3-L engines burning national average fuel on a simulated urban operating cycle. Exposure groups included whole exhaust diluted 1:10, 1:15, or 1:90, filtered exhaust at the 1:10 dilution, or clean air controls. Evaluations included organ weight, histopathology, hematology, serum chemistry, bronchoalveolar lavage, cardiac electrophysiology, micronuclei in circulating cells, DNA methylation and oxidative injury, clearance of Pseudomonas aeruginosa from the lung, and development of respiratory allergic responses to ovalbumin. Among the 120 outcome variables, only 20 demonstrated significant exposure effects. Several statistically significant effects appeared isolated and were not supported by related variables. The most coherent and consistent effects were those related to increased red blood cells, interpreted as likely to have resulted from exposure to 13-107 ppm carbon monoxide. Other effects supported by multiple variables included mild lung irritation and depression of oxidant production by alveolar macrophages. The lowest exposure level caused no significant effects. Because only 6 of the 20 significant effects appeared to be substantially reversed by PM filtration, the majority of effects were apparently caused by non-PM components of exhaust.

  13. Subchronic Inhalation Toxicity Study of n-pentane in Rats

    Directory of Open Access Journals (Sweden)

    Jong-Kyu Kim

    2012-09-01

    Conclusion: The no-observable-adverse-effect level (NOAEL of n-pentane is evaluated as being more than 6,885 ppm (20.3 mg/L in both male and female rats. n-pentane was not a classified specific target organ toxicity in the globally harmonized classification system (GHS.

  14. Toxicity of the main electronic cigarette components, propylene glycol, glycerin, and nicotine, in Sprague-Dawley rats in a 90-day OECD inhalation study complemented by molecular endpoints.

    Science.gov (United States)

    Phillips, Blaine; Titz, Bjoern; Kogel, Ulrike; Sharma, Danilal; Leroy, Patrice; Xiang, Yang; Vuillaume, Grégory; Lebrun, Stefan; Sciuscio, Davide; Ho, Jenny; Nury, Catherine; Guedj, Emmanuel; Elamin, Ashraf; Esposito, Marco; Krishnan, Subash; Schlage, Walter K; Veljkovic, Emilija; Ivanov, Nikolai V; Martin, Florian; Peitsch, Manuel C; Hoeng, Julia; Vanscheeuwijck, Patrick

    2017-11-01

    While the toxicity of the main constituents of electronic cigarette (ECIG) liquids, nicotine, propylene glycol (PG), and vegetable glycerin (VG), has been assessed individually in separate studies, limited data on the inhalation toxicity of them is available when in mixtures. In this 90-day subchronic inhalation study, Sprague-Dawley rats were nose-only exposed to filtered air, nebulized vehicle (saline), or three concentrations of PG/VG mixtures, with and without nicotine. Standard toxicological endpoints were complemented by molecular analyses using transcriptomics, proteomics, and lipidomics. Compared with vehicle exposure, the PG/VG aerosols showed only very limited biological effects with no signs of toxicity. Addition of nicotine to the PG/VG aerosols resulted in effects in line with nicotine effects observed in previous studies, including up-regulation of xenobiotic enzymes (Cyp1a1/Fmo3) in the lung and metabolic effects, such as reduced serum lipid concentrations and expression changes of hepatic metabolic enzymes. No toxicologically relevant effects of PG/VG aerosols (up to 1.520  mg PG/L + 1.890 mg VG/L) were observed, and no adverse effects for PG/VG/nicotine were observed up to 438/544/6.6 mg/kg/day. This study demonstrates how complementary systems toxicology analyses can reveal, even in the absence of observable adverse effects, subtoxic and adaptive responses to pharmacologically active compounds such as nicotine. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Green toxicology.

    Science.gov (United States)

    Maertens, Alexandra; Anastas, Nicholas; Spencer, Pamela J; Stephens, Martin; Goldberg, Alan; Hartung, Thomas

    2014-01-01

    Historically, early identification and characterization of adverse effects of industrial chemicals was difficult because conventional toxicological test methods did not meet R&D needs for rapid, relatively inexpensive methods amenable to small amounts of test material. The pharmaceutical industry now front-loads toxicity testing, using in silico, in vitro, and less demanding animal tests at earlier stages of product development to identify and anticipate undesirable toxicological effects and optimize product development. The Green Chemistry movement embraces similar ideas for development of less toxic products, safer processes, and less waste and exposure. Further, the concept of benign design suggests ways to consider possible toxicities before the actual synthesis and to apply some structure/activity rules (SAR) and in silico methods. This requires not only scientific development but also a change in corporate culture in which synthetic chemists work with toxicologists. An emerging discipline called Green Toxicology (Anastas, 2012) provides a framework for integrating the principles of toxicology into the enterprise of designing safer chemicals, thereby minimizing potential toxicity as early in production as possible. Green Toxicology`s novel utility lies in driving innovation by moving safety considerations to the earliest stage in a chemical`s lifecycle, i.e., to molecular design. In principle, this field is no different than other subdisciplines of toxicology that endeavor to focus on a specific area - for example, clinical, environmental or forensic toxicology. We use the same principles and tools to evaluate an existing substance or to design a new one. The unique emphasis is in using 21st century toxicology tools as a preventative strategy to "design out" undesired human health and environmental effects, thereby increasing the likelihood of launching a successful, sustainable product. Starting with the formation of a steering group and a series of workshops

  16. Forensic toxicology.

    Science.gov (United States)

    Davis, Gregory G

    2012-01-01

    Toxicologic analysis is an integral part of death investigation, and the use or abuse of an unsuspected substance belongs in the differential diagnosis of patients who have a sudden, unexpected change in their condition. History and physical findings may alter suspicion that intoxication played a role in a patient's decline or death, but suspicions cannot be confirmed and is performed, analysis unless toxicologic no toxicologic analysis is possible unless someone collects the proper specimens necessary for analysis. In a hospital autopsy the only specimens that can rightfully be collected are those within the restrictions stated in the autopsy permit. Autopsies performed by the medical examiner do not have these restrictions. Sometimes the importance of toxicologic testing in a case is not evident until days or weeks after the change in the patient's status, thus retaining the appropriate specimens until investigation of that case has ended is important. Proper interpretation of toxicologic findings requires integrating the clinical setting and findings with the toxicologic results in a way that makes medical sense. If called upon to testify concerning findings, answer the questions truthfully, politely, and in a way that is understandable to someone who has no special training in toxicology.

  17. Inhalation Toxicology of Fog Oil Smoke

    Science.gov (United States)

    1986-12-01

    PROLO) program (Russell et al., 1977). The 2.0-hr data suffered from heterogeneity of variance. The 6.0-hr data reflected too high an index of...CcwartiuLcWt fcrs, rtio lw x ur aptct Vtitv , klci utbhj" ctt. U S ft vtttltp 350 4) 3--0 Study AF J5--4 Study B 250 A-Combined Studies Aand B*. 150 1 300 -600

  18. Acute and subchronic toxicity analysis of surface modified paclitaxel attached hydroxyapatite and titanium dioxide nanoparticles

    Science.gov (United States)

    Venkatasubbu, Gopinath Devanand; Ramasamy, S; Gaddam, Pramod Reddy; Kumar, J

    2015-01-01

    Nanoparticles are widely used for targeted drug delivery applications. Surface modification with appropriate polymer and ligands is carried out to target the drug to the affected area. Toxicity analysis is carried out to evaluate the safety of the surface modified nanoparticles. In this study, paclitaxel attached, folic acid functionalized, polyethylene glycol modified hydroxyapatite and titanium dioxide nanoparticles were used for targeted drug delivery system. The toxicological behavior of the system was studied in vivo in rats and mice. Acute and subchronic studies were carried out. Biochemical, hematological, and histopathological analysis was also done. There were no significant alterations in the biochemical parameters at a low dosage. There was a small change in alkaline phosphatase (ALP) level at a high dosage. The results indicate a safe toxicological profile. PMID:26491315

  19. Toxicological Benchmarks for Wildlife

    Energy Technology Data Exchange (ETDEWEB)

    Sample, B.E. Opresko, D.M. Suter, G.W.

    1993-01-01

    Ecological risks of environmental contaminants are evaluated by using a two-tiered process. In the first tier, a screening assessment is performed where concentrations of contaminants in the environment are compared to no observed adverse effects level (NOAEL)-based toxicological benchmarks. These benchmarks represent concentrations of chemicals (i.e., concentrations presumed to be nonhazardous to the biota) in environmental media (water, sediment, soil, food, etc.). While exceedance of these benchmarks does not indicate any particular level or type of risk, concentrations below the benchmarks should not result in significant effects. In practice, when contaminant concentrations in food or water resources are less than these toxicological benchmarks, the contaminants may be excluded from further consideration. However, if the concentration of a contaminant exceeds a benchmark, that contaminant should be retained as a contaminant of potential concern (COPC) and investigated further. The second tier in ecological risk assessment, the baseline ecological risk assessment, may use toxicological benchmarks as part of a weight-of-evidence approach (Suter 1993). Under this approach, based toxicological benchmarks are one of several lines of evidence used to support or refute the presence of ecological effects. Other sources of evidence include media toxicity tests, surveys of biota (abundance and diversity), measures of contaminant body burdens, and biomarkers. This report presents NOAEL- and lowest observed adverse effects level (LOAEL)-based toxicological benchmarks for assessment of effects of 85 chemicals on 9 representative mammalian wildlife species (short-tailed shrew, little brown bat, meadow vole, white-footed mouse, cottontail rabbit, mink, red fox, and whitetail deer) or 11 avian wildlife species (American robin, rough-winged swallow, American woodcock, wild turkey, belted kingfisher, great blue heron, barred owl, barn owl, Cooper's hawk, and red

  20. Haematogical changes induced by subchronic glyphosate exposure ...

    African Journals Online (AJOL)

    The aim of this study was to determine the haematological changes induced by subchronic glyphosate exposure in Wistar rats and the ameliorative effect of zinc. Sixty adult male and female Wistar rats were used for the study. Twelve of them were used for the LD50 which was evaluated to be 3750 mg kg-1 with clinical ...

  1. Space Toxicology: Human Health during Space Operations

    Science.gov (United States)

    Khan-Mayberry, Noreen; James, John T.; Tyl, ROchelle; Lam, Chiu-Wing

    2010-01-01

    Space Toxicology is a unique and targeted discipline for spaceflight, space habitation and occupation of celestial bodies including planets, moons and asteroids. Astronaut explorers face distinctive health challenges and limited resources for rescue and medical care during space operation. A central goal of space toxicology is to protect the health of the astronaut by assessing potential chemical exposures during spaceflight and setting safe limits that will protect the astronaut against chemical exposures, in a physiologically altered state. In order to maintain sustained occupation in space on the International Space Station (ISS), toxicological risks must be assessed and managed within the context of isolation continuous exposures, reuse of air and water, limited rescue options, and the need to use highly toxic compounds for propulsion. As we begin to explore other celestial bodies in situ toxicological risks, such as inhalation of reactive mineral dusts, must also be managed.

  2. Toxicological Evaluation of Lactase Derived from Recombinant Pichia pastoris

    Science.gov (United States)

    Liu, Yifei; Chen, Delong; Luo, Yunbo; Huang, Kunlun; Zhang, Wei; Xu, Wentao

    2014-01-01

    A recombinant lactase was expressed in Pichia pastoris, resulting in enzymatic activity of 3600 U/mL in a 5 L fermenter. The lactase product was subjected to a series of toxicological tests to determine its safety for use as an enzyme preparation in the dairy industry. This recombinant lactase had the highest activity of all recombinant strains reported thus far. Acute oral toxicity, mutagenicity, genotoxic, and subchronic toxicity tests performed in rats and mice showed no death in any groups. The lethal dose 50% (LD50) based on the acute oral toxicity study is greater than 30 mL/kg body weight, which is in accordance with the 1500 L milk consumption of a 50 kg human daily. The lactase showed no mutagenic activity in the Ames test or a mouse sperm abnormality test at levels of up to 5 mg/plate and 1250 mg/kg body weight, respectively. It also showed no genetic toxicology in a bone marrow cell micronucleus test at levels of up to 1250 mg/kg body weight. A 90-day subchronic repeated toxicity study via the diet with lactase levels up to 1646 mg/kg (1000-fold greater than the mean human exposure) did not show any treatment-related significant toxicological effects on body weight, food consumption, organ weights, hematological and clinical chemistry, or histopathology compared to the control groups. This toxicological evaluation system is comprehensive and can be used in the safety evaluation of other enzyme preparations. The lactase showed no acute, mutagenic, genetic, or subchronic toxicity under our evaluation system. PMID:25184300

  3. Toxicological evaluation of lactase derived from recombinant Pichia pastoris.

    Directory of Open Access Journals (Sweden)

    Shiying Zou

    Full Text Available A recombinant lactase was expressed in Pichia pastoris, resulting in enzymatic activity of 3600 U/mL in a 5 L fermenter. The lactase product was subjected to a series of toxicological tests to determine its safety for use as an enzyme preparation in the dairy industry. This recombinant lactase had the highest activity of all recombinant strains reported thus far. Acute oral toxicity, mutagenicity, genotoxic, and subchronic toxicity tests performed in rats and mice showed no death in any groups. The lethal dose 50% (LD50 based on the acute oral toxicity study is greater than 30 mL/kg body weight, which is in accordance with the 1500 L milk consumption of a 50 kg human daily. The lactase showed no mutagenic activity in the Ames test or a mouse sperm abnormality test at levels of up to 5 mg/plate and 1250 mg/kg body weight, respectively. It also showed no genetic toxicology in a bone marrow cell micronucleus test at levels of up to 1250 mg/kg body weight. A 90-day subchronic repeated toxicity study via the diet with lactase levels up to 1646 mg/kg (1000-fold greater than the mean human exposure did not show any treatment-related significant toxicological effects on body weight, food consumption, organ weights, hematological and clinical chemistry, or histopathology compared to the control groups. This toxicological evaluation system is comprehensive and can be used in the safety evaluation of other enzyme preparations. The lactase showed no acute, mutagenic, genetic, or subchronic toxicity under our evaluation system.

  4. TOXNET: Toxicology Data Network

    Science.gov (United States)

    ... to TOXNET Your resource for searching databases on toxicology, hazardous chemicals, environmental health, and toxic releases SEARCH ... over 3,000 chemicals (1991-1998) Environmental Health & Toxicology Resources on environmental health and toxicology Visit Site ...

  5. Acute and subchronic oral toxicity studies in rats of a hydrolyzed chicken sternal cartilage preparation.

    Science.gov (United States)

    Schauss, A G; Merkel, D J; Glaza, S M; Sorenson, S R

    2007-02-01

    Two acute and subchronic oral toxicity studies were conducted in rats to evaluate safety of a patented preparation of hydrolyzed chicken sternal cartilage (BioCell Collagen II) containing collagen type II, chondroitin sulfate, and hyaluronic acid. In the acute oral toxicity study, five males and five females of Sprague-Dawley rats were administered a single dose of 5000 mg of the test product per kg body weight and observed for 14 days. All animals survived and exhibited normal body weight gain throughout the study. Macroscopic necropsy examination conducted on day 15 revealed no gross pathological lesions in any of the animals. In the subchronic study, Sprague-Dawley rats (40 males, 40 females) were divided into four same-sex groups (10 animals/group). Animals in each group were administered daily either 0, 30, 300 or 1000 mg of the test product per kg of body weight for over 90 days. All animals survived and showed no significant changes in their body weights and histopathology. Although some differences were observed between the treated and control animals in several parameters, they were generally not dose-related or considered to be of toxicological significance. In conclusion, the results from the two oral toxicity studies with male and female young adult rats indicated that the test preparation from hydrolyzed chicken sternal cartilage collagen (BioCell Collagen II) was well tolerated at all four doses tested.

  6. Space Toxicology

    Science.gov (United States)

    James, John T.

    2011-01-01

    Safe breathing air for space faring crews is essential whether they are inside an Extravehicular Mobility Suit (EMU), a small capsule such as Soyuz, or the expansive International Space Station (ISS). Sources of air pollution can include entry of propellants, excess offgassing from polymeric materials, leakage of systems compounds, escape of payload compounds, over-use of utility compounds, microbial metabolism, and human metabolism. The toxicological risk posed by a compound is comprised of the probability of escaping to cause air pollution and the magnitude of adverse effects on human health if escape occurs. The risk from highly toxic compounds is controlled by requiring multiple levels of containment to greatly reduce the probability of escape; whereas compounds that are virtually non-toxic may require little or no containment. The potential for toxicity is determined by the inherent toxicity of the compound and the amount that could potentially escape into the breathing air.

  7. Animal toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Amdur, M.

    1996-12-31

    The chapter evaluates results of toxicological studies on experimental animals to investigate health effects of air pollutants and examines the animal data have predicted the response to human subject. Data are presented on the comparative toxicity of sulfur dioxide and sulfuric acid. The animal data obtained by measurement of airway resistance in guinea pigs and of bronchial clearance of particles in donkeys predicted clearly that sulfuric acid was more irritant than sulfur dioxide. Data obtained on human subjects confirmed this prediction. These acute studies also correctly predicted the comparative toxicity of the two compounds in two year studies of monkeys. Such chronic studies are not possible in human subjects but it is a reasonable to assume that sulfuric acid would be more toxic than sulfur dioxide. Current findings in epidemiological studies certainly support this assumption.

  8. Forensic Toxicology: An Introduction.

    Science.gov (United States)

    Smith, Michael P; Bluth, Martin H

    2016-12-01

    This article presents an overview of forensic toxicology. The authors describe the three components that make up forensic toxicology: workplace drug testing, postmortem toxicology, and human performance toxicology. Also discussed are the specimens that are tested, the methods used, and how the results are interpreted in this particular discipline. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Safety assessment of Superba™ krill powder: Subchronic toxicity study in rats

    Directory of Open Access Journals (Sweden)

    Kjetil Berge

    2015-01-01

    Full Text Available The safety of krill powder was assessed in a subchronic 13-week toxicity study where rats were fed krill powder or control diets. The krill powder inclusion in the test diet was 9.67% (w/w. There were no differences noted in body weight or food consumption in either gender. Differences in clinical chemistry values were noted in the krill powder-treated animals, but these findings were of no toxicological significance. A significant decrease in absolute heart weight, but not relative heart weight, was observed in both sexes given krill powder, although no corresponding histological changes were observed. Hepatocyte vacuolation was noted histologically in males fed krill powder. This finding was not associated with other indications of hepatic dysfunction. The no observed adverse effect level (NOAEL for the conditions of this study was considered to be 9.67% krill powder.

  10. How subchronic and chronic health effects can be neglected for GMOs, pesticides or chemicals.

    Science.gov (United States)

    Séralini, Gilles-Eric; de Vendômois, Joël Spiroux; Cellier, Dominique; Sultan, Charles; Buiatti, Marcello; Gallagher, Lou; Antoniou, Michael; Dronamraju, Krishna R

    2009-06-17

    Chronic health effects are increasing in the world such as cancers, hormonal, reproductive, nervous, or immune diseases, even in young people. During regulatory toxicological subchronic tests to prevent these on mammalian health, prior commercialization of chemicals, including pesticides and drugs, or GMOs, some statistically significant findings may be revealed. This discussion is about the need to investigate the relevant criteria to consider those as biologically significant. The sex differences and the non linear dose or time related effects should be considered in contrast to the claims of a Monsanto-supported expert panel about a GMO, the MON 863 Bt maize, but also for pesticides or drugs, in particular to reveal hormone-dependent diseases and first signs of toxicities.

  11. A Review of the Comparative Anatomy, Histology, Physiology and Pathology of the Nasal Cavity of Rats, Mice, Dogs and Non-human Primates. Relevance to Inhalation Toxicology and Human Health Risk Assessment.

    Science.gov (United States)

    Chamanza, R; Wright, J A

    2015-11-01

    There are many significant differences in the structural and functional anatomy of the nasal cavity of man and laboratory animals. Some of the differences may be responsible for the species-specific nasal lesions that are often observed in response to inhaled toxicants. This paper reviews the comparative anatomy, physiology and pathology of the nasal cavity of the rat, mouse, dog, monkey and man, highlighting factors that may influence the distribution of nasal lesions. Gross anatomical variations such as turbinate structure, folds or grooves on nasal walls, or presence or absence of accessory structures, may influence nasal airflow and species-specific uptake and deposition of inhaled material. In addition, interspecies variations in the morphological and biochemical composition and distribution of the nasal epithelium may affect the local tissue susceptibility and play a role in the development of species-specific nasal lesions. It is concluded that, while the nasal cavity of the monkey might be more similar to that of man, each laboratory animal species provides a model that responds in a characteristic and species-specific manner. Therefore for human risk assessment, careful consideration must be given to the anatomical differences between a given animal model and man. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Decreased Hippocampal Neuroplasticity and Behavioral Impairment in an Animal Model of Inhalant Abuse

    Directory of Open Access Journals (Sweden)

    Hanaa Malloul

    2018-02-01

    Full Text Available Thinners are highly toxic chemicals widely employed as organic solvents in industrial and domestic use. They have psychoactive properties when inhaled, and their chronic abuse as inhalants is associated with severe long-term health effects, including brain damage and cognitive-behavioral alterations. Yet, the sites and mechanisms of action of these compounds on the brain are far from being fully understood. Here, we investigated the consequences of paint thinner inhalation in adult male mice. Depression-like behaviors and an anxiolytic effect were found following repeated exposure in chronic treatments lasting 12 weeks. Both subchronic (6 weeks and chronic treatments impaired learning and memory functions, while no changes were observed after acute treatment. To investigate possible molecular/structural alterations underlying such behavioral changes, we focused on the hippocampus. Notably, prolonged, but not acute thinner inhalation strongly affected adult neurogenesis in the dentate gyrus (DG, reducing progenitor cell proliferation after chronic treatments and impairing the survival of newborn neurons following both chronic and subchronic treatments. Furthermore, a down-regulation in the expression of BDNF and NMDA receptor subunits as well as a reduction in CREB expression/phosphorylation were found in the hippocampi of chronically treated mice. Our findings demonstrate for the first time significant structural and molecular changes in the adult hippocampus after prolonged paint thinner inhalation, indicating reduced hippocampal neuroplasticity and strongly supporting its implication in the behavioral dysfunctions associated to inhalant abuse.

  13. Human lung epithelial cell cultures for analysis of inhaled toxicants: Lessons learned and future directions

    NARCIS (Netherlands)

    Hiemstra, P.S.; Grootaers, G.G.; Does, A.M. van der; Krul, C.A.M.; Kooter, I.M.

    2018-01-01

    The epithelium that covers the conducting airways and alveoli is a primary target for inhaled toxic substances, and therefore a focus in inhalation toxicology. The increasing concern about the use of animal models has stimulated the development of in vitro cell culture models for analysis of the

  14. Cornerstones of Toxicology.

    Science.gov (United States)

    Hayes, A Wallace; Dixon, Darlene

    2017-01-01

    The 35th Annual Society of Toxicologic Pathology Symposium, held in June 2016 in San Diego, California, focused on "The Basis and Relevance of Variation in Toxicologic Responses." In order to review the basic tenants of toxicology, a "broad brush" interactive talk that gave an overview of the Cornerstones of Toxicology was presented. The presentation focused on the historical milestones and perspectives of toxicology and through many scientific graphs, data, and real-life examples covered the three basic principles of toxicology that can be summarized, as dose matters (as does timing), people differ, and things change (related to metabolism and biotransformation).

  15. National Toxicology Program

    Science.gov (United States)

    ... NTP? NTP develops and applies tools of modern toxicology and molecular biology to identify substances in the ... depend on for decisions that matter. The National Toxicology Program provides the scientific basis for programs, activities, ...

  16. Toxicology Education Foundation

    Science.gov (United States)

    ... bodies and our world. Welcome to the Toxicology Education Foundation! Our mission is to enhance public understanding ... In with us, follow our Tweets, choose Toxicology Education Foundation as your preferred charity through Smile.Amazon. ...

  17. Environmental Toxicology Research Facility

    Data.gov (United States)

    Federal Laboratory Consortium — Fully-equipped facilities for environmental toxicology researchThe Environmental Toxicology Research Facility (ETRF) located in Vicksburg, MS provides over 8,200 ft...

  18. Handbook of systems toxicology

    National Research Council Canada - National Science Library

    Casciano, Daniel A; Sahu, Saura C

    2011-01-01

    "In the first handbook to comprehensively cover the emerging area of systems toxicology, the Handbook of Systems Toxicology provides an authoritative compilation of up-to-date developments presented...

  19. Green Toxicology – Application of predictive toxicology

    DEFF Research Database (Denmark)

    Vinggaard, Anne Marie; Wedebye, Eva Bay; Taxvig, Camilla

    2014-01-01

    safer chemicals and to identify problematic compounds already in use such as industrial compounds, drugs, pesticides and cosmetics, is required. Green toxicology is the application of predictive toxicology to the production of chemicals with the specific intent of improving their design for hazard...

  20. Polymer degradation and ultrafine particles - Potential inhalation hazards for astronauts

    Science.gov (United States)

    Ferin, J.; Oberdoerster, G.

    1992-01-01

    To test the hypothesis that exposure to ultrafine particles results in an increased interstiatilization of the particles which is accompanied by an acute pathological inflammation, rats were exposed to titanium dioxide (TiO2) particles by intratracheal instillation and by inhalation. Both acute intratracheal instillation and subchronic inhalation studies on rats show that ultrafine TiO2 particles access the pulmonary interstitium to a larger extent than fine particles and that they elicit an inflammatory response as indicated by PMN increase in lavaged cells. The release of ultrafine particles into the air of an enclosed environment from a thermodegradation event or from other sources is a potential hazard for astronauts. Knowing the mechanisms of action is a prerequisite for technical or medical countermeasures.

  1. Inhalation Therapy in Horses.

    Science.gov (United States)

    Cha, Mandy L; Costa, Lais R R

    2017-04-01

    This article discusses the benefits and limitations of inhalation therapy in horses. Inhalation drug therapy delivers the drug directly to the airways, thereby achieving maximal drug concentrations at the target site. Inhalation therapy has the additional advantage of decreasing systemic side effects. Inhalation therapy in horses is delivered by the use of nebulizers or pressured metered dose inhalers. It also requires the use of a muzzle or nasal mask in horses. Drugs most commonly delivered through inhalation drug therapy in horses include bronchodilators, antiinflammatories, and antimicrobials. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. IRIS TOXICOLOGICAL REVIEW AND SUMMARY ...

    Science.gov (United States)

    The Draft Toxicological Review was developed to evaluate both the cancer and non cancer human health risks from environmental exposure to vinyl chloride. A reference concentration (RfC), and a reference dose (RfD) were developed based upon induction of liver cell polymorphism in a chronic dietary study utilizing Wistar rats. An RfC of 1E-1 mg/m3 and an RfD of 5E-3 mg/kg-d are recommended. On the basis of sufficient evidence for carcinogenicity in human epidemiology studies vinyl chloride is reaffirmed to be a known human carcinogen. Cancer potencies were derived for oral and inhalation exposure. An oral slope factor of 1.3 per (mg/kg-day) for continuous exposure during adulthood and 2.5 per (mg/kg-day) for continuous lifetime exposure from birth, based upon a chronic dietary study in female Wistar rats is recommended; an inhalation unit risk of 4.3 E-6 per (55g/m3) for continuous exposure during adulthood and 8.7 E-6 per (55g/m3) for continuous lifetime exposure from birth is also recommended, based upon exposure of male and female Sprague Dawley rats and Swiss mice, via inhalation, for a lifetime. A PBPK model was used in the derivation of the RfC, RfD, and cancer potency estimates. Its use is based on the assumption that equal tissue concentrations of reactive metabolite, chlorethylene oxide or chloracetaldehyde, at the critical target site will result in equivalent toxicity between species.

  3. Intestinal lymphangiectasis and lipidosis in rats following subchronic exposure to indole-3-carbinol via oral gavage.

    Science.gov (United States)

    Boyle, Michael C; Crabbs, Torrie A; Wyde, Michael E; Painter, J Todd; Hill, Georgette D; Malarkey, David E; Lieuallen, Warren G; Nyska, Abraham

    2012-06-01

    To investigate the toxicity and carcinogenic potential of indole-3-carbinol (I3C), the National Toxicology Program has conducted 13-week subchronic studies in Fisher 344 rats and B6C3F1 mice, and chronic 2-year bioassays in Sprague-Dawley rats and B6C3F1 mice. While the chronic study results are not yet available, subchronic study results and short-term special evaluations of interim sacrifices in the 2-year rat bioassay are presented. F344 rats were orally gavaged ≤300 mg I3C/kg body weight 5 days a week for 13 weeks. Rats treated with ≥150 mg/kg demonstrated a dose-related dilation of lymphatics (lymphangiectasis) of the duodenum, jejunum, and mesenteric lymph nodes. Material within dilated lacteals stained positively for Oil Red O and Sudan Black, consistent with lipid. Electron microscopic evaluation confirmed extracellular lipid accumulation within the villar lamina propria, lacteals, and within villar macrophages. Analyses of hepatic and pulmonary CYP1A enzymes demonstrated dose-dependent I3C induction of CYP1A1 and 1A2. B6C3F1 mice orally gavaged ≤250 mg I3C/kg body weight did not demonstrate histopathological changes; however, hepatic CYP induction was similar to that in rats. The histopathologic changes of intestinal lymphangiectasis and lipidosis in this study share similarities with intestinal lymphangiectasia as observed in humans and dogs. However, the resultant clinical spectrum of protein-losing enteropathy was not present.

  4. Institute for Genetics and Toxicology of Fission Materials. Annual report on research and development work in 1989

    International Nuclear Information System (INIS)

    1990-03-01

    The report covers the research results achieved in 1989 in the following subject fields: Gene repair and gene regulation, biological carcinogenesis, molecular genetics of eukaryontic genes, radiotoxicology of the actinides, cellular inhalation toxicology, cellular and molecular toxicology, and in vitro fractionation and speciation of actinides. A list of publications of the Institute in 1989 shows printed original reports and conference papers. (MG) [de

  5. Toxicity assessment of perfluorooctane sulfonate using acute and subchronic male C57BL/6J mouse models

    International Nuclear Information System (INIS)

    Xing, Jiali; Wang, Gang; Zhao, Jichun; Wang, Eryin; Yin, Boxing; Fang, Dongsheng; Zhao, Jianxin; Zhang, Hao; Chen, Yong Q.; Chen, Wei

    2016-01-01

    Perfluorooctane sulfonate (PFOS) is a principal representative and the final degradation product of several commercially produced perfluorinated compounds. However, PFOS has a high bioaccumulation potential and therefore can exert toxicity on aquatic organisms, animals, and cells. Considering the widespread concern this phenomenon has attracted, we examined the acute and subchronic toxic effects of varying doses of PFOS on adult male C57BL/6 mice. The acute oral LD_5_0 value of PFOS in male C57BL/6J mice was 0.579 g/kg body weight (BW). Exposure to the subchronic oral toxicity of PFOS at 2.5, 5, and 10 mg PFOS/kg BW/day for 30 days disrupted the homeostasis of antioxidative systems, induced hepatocellular apoptosis (as revealed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay), triggered liver injury (as evidenced by the increased serum levels of aspartate aminotransferase, alanine amino transferase, alkaline phosphatase, and gamma-glutamyl transpeptidase and by the altered histology), and ultimately increased the liver size and relative weight of the mice. PFOS treatment caused liver damage but only slightly affected the kidneys and spleen of the mice. This study provided insights into the toxicological effects of PFOS. - Highlights: • The acute and subchronic toxicity of PFOS was systematically investigated. • The acute oral LD_5_0 value for PFOS in C57BL/6J mice was 0.579 g/kg body weight. • PFOS disrupted the homeostasis of antioxidative systems. • PFOS induced hepatocellular apoptosis and triggered liver injury. - PFOS disrupted the homeostasis of antioxidative systems, induced hepatocellular apoptosis, and triggered liver injury.

  6. Ciclesonide Oral Inhalation

    Science.gov (United States)

    ... use ciclesonide inhalation.Ciclesonide inhalation helps to prevent asthma attacks (sudden episodes of shortness of breath, wheezing, and coughing) but will not stop an asthma attack that has already started. Do not use ciclesonide ...

  7. Flunisolide Oral Inhalation

    Science.gov (United States)

    ... use flunisolide inhalation.Flunisolide inhalation helps to prevent asthma attacks (sudden episodes of shortness of breath, wheezing, and coughing) but will not stop an asthma attack that has already started. Do not use flunisolide ...

  8. IRIS Toxicological Review of Dichloromethane (Methylene ...

    Science.gov (United States)

    EPA has finalized the Toxicological Review of Dichloromethane (Methylene Chloride): In support of the Integrated Risk Information System (IRIS). Now final, this assessment may be used by EPA’s program and regional offices to inform decisions to protect human health. This document presents background information and justification for the Intergrated Risk Information System (IRIS) Summary of the hazard and dose-response assessment of dichloromethane. IRIS Summaries may include oral reference dose (RfD) and inhalation reference concentration (RfC) values for chronic and other exposure durations, and a carcinogencity assessment. Internet/NCEA web site

  9. Hydrazine inhalation hepatotoxicity.

    Science.gov (United States)

    Kao, Yung Hsiang; Chong, C H; Ng, W T; Lim, D

    2007-10-01

    Abstract Hydrazine is a hazardous chemical commonly used as a reactant in rocket and jet fuel cells. Animal studies have demonstrated hepatic changes after hydrazine inhalation. Human case reports of hydrazine inhalation hepatotoxicity are rare. We report a case of mild hepatotoxicity following brief hydrazine vapour inhalation in a healthy young man, which resolved completely on expectant management.

  10. Genotoxicity, acute and subchronic toxicity studies in rats of a rooster comb extract rich in sodium hyaluronate.

    Science.gov (United States)

    Canut, Lourdes; Zapatero, Jorge; López, Sílvia; Torrent, Anna; Ruhí, Ramon; Vicente, Laura

    2012-04-01

    The toxicity of a rooster comb extract (IB0004) that contains mainly sodium hyaluronate was assessed in acute and subchronic studies and in a bacterial reverse mutation assay. In a single dose acute study, male and female rats were administered 2000 mg/kg body weight (bw) of the product and observed for 14 days. No mortality was recorded, thus it was considered that the minimum lethal dose for rats by oral route was greater than 2000 mg/kg bw. A 90-day subchronic study (5, 55 and 600 mg/kg bw/day, oral gavage) with 50 male and 50 female Wistar-Hannover rats produced no significant adverse effects on food consumption, body weight, mortality, clinical biochemistry, hematology, gross pathology, and histopathology. Although some differences were observed between the treated and control animals in body weight gain (%) and some hematological parameters, these changes were generally minor in nature and, are considered to be of no toxicological significance. The no-observable-adverse-effects level was established at 600 mg/kg bw/day. There was no evidence of mutagenic activity in Salmonella typhimurium TA98, TA100, TA1535 and TA1537 or in Escherichia coli WP2 uvra pkM101. In conclusion, the results from these safety studies support the safety of rooster comb extract IB0004 in food. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Safety assessment of non-animal chondroitin sulfate sodium: Subchronic study in rats, genotoxicity tests and human bioavailability.

    Science.gov (United States)

    Miraglia, Niccolò; Bianchi, Davide; Trentin, Antonella; Volpi, Nicola; Soni, Madhu G

    2016-07-01

    Chondroitin sulfate, an amino sugar polymer made of glucuronic acid and N-acetyl-galactosamine, is used in dietary supplements to promote joint health. Commonly used chondroitin sulfate is of animal origin and can pose potential safety problems including bovine spongiform encephalopathy (BSE). The objective of the present study was to investigate potential adverse effects, if any, of microbial derived chondroitin sulfate sodium (CSS) in subchronic toxicity, genotoxicity and bioavailability studies. In the toxicity study, Sprague Dawley rats (10/sex/group) were gavaged with CSS at dose levels of 0, 250, 500 and 1000 mg/kg body weight (bw)/day for 90-days. No mortality or significant changes in clinical signs, body weights, body weight gain or feed consumption were noted. Similarly, no toxicologically relevant treatment-related changes in hematological, clinical chemistry, urinalysis and organ weights were noted. Macroscopic and microscopic examinations did not reveal treatment-related abnormalities. In vitro mutagenic and clastogenic potentials as evaluated by Ames assay, chromosomal aberration test and micronucleus assay did not reveal genotoxicity of CSS. In pharmacokinetic study in human, CSS showed higher absorption as compared to chondroitin sulfate of animal origin. The results of subchronic toxicity study supports the no-observed-adverse-effect level (NOAEL) for CSS as 1000 mg/kg bw/day, the highest dose tested. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Effect of Nano-sized Carbon Black Particles on Lung and Circulatory System by Inhalation Exposure in Rats

    Directory of Open Access Journals (Sweden)

    Jong-Kyu Kim

    2011-09-01

    Conclusion: We successfully generated nano-CBPs in the range of 83.3-87.9 nm at a maximum concentration of 4.2 × 106 particles/cm3 in a nose-only inhalation chamber system. This reliable method can be useful to investigate the biological and toxicological effects of inhalation exposure to nano-CBPs on experimental rats.

  13. Reproductive and developmental toxicology

    National Research Council Canada - National Science Library

    Gupta, Ramesh C

    2011-01-01

    .... Reproductive and Developmental Toxicology is a comprehensive and authoritative resource providing the latest literature enriched with relevant references describing every aspect of this area of science...

  14. Toxicological assessment of polyhexamethylene biguanide for water treatment

    Directory of Open Access Journals (Sweden)

    Asiedu-Gyekye Isaac J.

    2015-12-01

    Full Text Available Polyhexamethylene biguanide (PHMB is an antiseptic with antiviral and antibacterial properties used in a variety of products including wound care dressings, contact lens cleaning solutions, perioperative cleansing products, and swimming pool cleaners. There are regulatory concerns with regard to its safety in humans for water treatment. We decided to assess the safety of this chemical in Sprague-Dawley rats. PHMB was administered in a single dose by gavage via a stomach tube as per the manufacturer’s instruction within a dose range of 2 mg/kg to 40 mg/kg. Subchronic toxicity studies were also conducted at doses of 2 mg/kg, 8 mg/kg and 32 mg/kg body weight and hematological, biochemical and histopathological findings of the major organs were assessed. Administration of a dose of 25.6 mg/kg, i.e. 1.6 mL of 0.4% PHMB solution (equivalent to 6.4×103 mg/L of 0.1% solution resulted in 50% mortality. Histopathological analysis in the acute toxicity studies showed that no histopathological lesions were observed in the heart and kidney samples but 30% of the animals had mild hydropic changes in zone 1 of their liver samples, while at a dosage of 32 mg/kg in the subchronic toxicity studies, 50% of the animals showed either mild hepatocyte cytolysis with or without lymphocyte infiltration and feathery degeneration. Lymphocyte infiltration was, for the first time, observed in one heart sample, whereas one kidney sample showed mild tubular damage. The acute studies showed that the median lethal dose (LD50 is 25.6 mg/kg (LC50 of 1.6 mL of 0.4% PHMB. Subchronic toxicological studies also revealed few deleterious effects on the internal organs examined, as seen from the results of the biochemical parameters evaluated. These results have implications for the use of PHMB to make water potable.

  15. Fossil fuel toxicology

    International Nuclear Information System (INIS)

    Anon.

    1976-01-01

    A program is described for the investigation of the toxicology of coal-derived effluents that will utilize a battery of cellular and mammalian test systems and end points to evaluate the toxicological effects of acute, sub-acute, and long-term, low-level exposure to gaseous and particulate effluents from combustion of coal, with special emphasis on fluidized bed combustion

  16. Toxicology ontology perspectives.

    Science.gov (United States)

    Hardy, Barry; Apic, Gordana; Carthew, Philip; Clark, Dominic; Cook, David; Dix, Ian; Escher, Sylvia; Hastings, Janna; Heard, David J; Jeliazkova, Nina; Judson, Philip; Matis-Mitchell, Sherri; Mitic, Dragana; Myatt, Glenn; Shah, Imran; Spjuth, Ola; Tcheremenskaia, Olga; Toldo, Luca; Watson, David; White, Andrew; Yang, Chihae

    2012-01-01

    The field of predictive toxicology requires the development of open, public, computable, standardized toxicology vocabularies and ontologies to support the applications required by in silico, in vitro, and in vivo toxicology methods and related analysis and reporting activities. In this article we review ontology developments based on a set of perspectives showing how ontologies are being used in predictive toxicology initiatives and applications. Perspectives on resources and initiatives reviewed include OpenTox, eTOX, Pistoia Alliance, ToxWiz, Virtual Liver, EU-ADR, BEL, ToxML, and Bioclipse. We also review existing ontology developments in neighboring fields that can contribute to establishing an ontological framework for predictive toxicology. A significant set of resources is already available to provide a foundation for an ontological framework for 21st century mechanistic-based toxicology research. Ontologies such as ToxWiz provide a basis for application to toxicology investigations, whereas other ontologies under development in the biological, chemical, and biomedical communities could be incorporated in an extended future framework. OpenTox has provided a semantic web framework for the implementation of such ontologies into software applications and linked data resources. Bioclipse developers have shown the benefit of interoperability obtained through ontology by being able to link their workbench application with remote OpenTox web services. Although these developments are promising, an increased international coordination of efforts is greatly needed to develop a more unified, standardized, and open toxicology ontology framework.

  17. Toxicological assessment of nattokinase derived from Bacillus subtilis var. natto.

    Science.gov (United States)

    Lampe, Bradley J; English, J Caroline

    2016-02-01

    Subtilisin NAT, commonly known as "nattokinase," is a fibrinolytic enzyme produced by the bacterial strain B. subtilis var. natto, which plays a central role in the fermentation of soybeans into the popular Japanese food natto. Recent studies have reported on the potential anticoagulatory and antihypertensive effects of nattokinase administration in humans, with no indication of adverse effects. To evaluate the safety of nattokinase in a more comprehensive manner, several GLP-compliant studies in rodents and human volunteers have been conducted with the enzyme product, NSK-SD (Japan Bio Science Laboratory Co., Ltd., Japan). Nattokinase was non-mutagenic and non-clastogenic in vitro, and no adverse effects were observed in 28-day and 90-day subchronic toxicity studies conducted in Sprague-Dawley rats at doses up to 167 mg/kg-day and 1000 mg/kg-day, respectively. Mice inoculated with 7.55 × 10(8) CFU of the enzyme-producing bacterial strain showed no signs of toxicity or residual tissue concentrations of viable bacteria. Additionally consumption of 10 mg/kg-day nattokinase for 4 weeks was well tolerated in healthy human volunteers. These findings suggest that the oral consumption of nattokinase is of low toxicological concern. The 90-day oral subchronic NOAEL for nattokinase in male and female Sprague-Dawley rats is 1000 mg/kg-day, the highest dose tested. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Toxicology Studies on Lewisite and Sulfur Mustard Agents: Subchronic Toxicity Study of Lewisite in Rats

    Science.gov (United States)

    1989-07-31

    buffered formalin (NBF). To standardize the degree of distension of pulmonary alveoli with fixative, the lungs were fixed by inserting a blunted needle into...the thickness of the mucosa, submucosa and muscular layers of the stomach and involved the serosa. Epithelial hyperplasia and hyperkeratosis of the

  19. Evidence-Based Toxicology.

    Science.gov (United States)

    Hoffmann, Sebastian; Hartung, Thomas; Stephens, Martin

    Evidence-based toxicology (EBT) was introduced independently by two groups in 2005, in the context of toxicological risk assessment and causation as well as based on parallels between the evaluation of test methods in toxicology and evidence-based assessment of diagnostics tests in medicine. The role model of evidence-based medicine (EBM) motivated both proposals and guided the evolution of EBT, whereas especially systematic reviews and evidence quality assessment attract considerable attention in toxicology.Regarding test assessment, in the search of solutions for various problems related to validation, such as the imperfectness of the reference standard or the challenge to comprehensively evaluate tests, the field of Diagnostic Test Assessment (DTA) was identified as a potential resource. DTA being an EBM discipline, test method assessment/validation therefore became one of the main drivers spurring the development of EBT.In the context of pathway-based toxicology, EBT approaches, given their objectivity, transparency and consistency, have been proposed to be used for carrying out a (retrospective) mechanistic validation.In summary, implementation of more evidence-based approaches may provide the tools necessary to adapt the assessment/validation of toxicological test methods and testing strategies to face the challenges of toxicology in the twenty first century.

  20. A novel nasal powder formulation of glucagon: toxicology studies in animal models

    OpenAIRE

    Reno, Frederick E.; Normand, Patrick; McInally, Kevin; Silo, Sherwin; Stotland, Patricia; Triest, Myriam; Carballo, Dolores; Pich?, Claude

    2015-01-01

    Background Glucagon nasal powder (GNP), a novel intranasal formulation of glucagon being developed to treat insulin-induced severe hypoglycemia, contains synthetic glucagon (10?% w/w), beta-cyclodextrin, and dodecylphosphocholine. The safety of this formulation was evaluated in four studies in animal models. Methods The first study evaluated 28-day sub-chronic toxicology in rats treated intranasally with 1 and 2?mg of GNP/day (0.1 and 0.2?mg glucagon/rat/day). The second study evaluated 28-da...

  1. Inhalation developmental toxicology studies: Acetonitrile in rats. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Mast, T.J.; Weigel, R.J.; Westerberg, R.B.; Boyd, P.J.; Hayden, B.K.; Evanoff, J.J.; Rommereim, R.L.

    1994-02-01

    The potential for acetonitrile to cause developmental toxicity was assessed in Sprague-Dawley rats exposed to 0, 100, 400, or 1200 ppM acetonitrile, 6 hours/day, 7 days/week. Exposure of rats to these concentrations of acetonitrile resulted in mortality in the 1200 ppM group (2/33 pregnant females; 1/10 non-pregnant females). However, there were no treatment-related effects upon body weights or reproduction indices at any exposure level, nor was there a significant increase in the incidence of fetal malformations or variations. The only effect observed in the fetuses was a slight, but not statiscally significant, exposure-correlated increase in the incidence of supernumerary ribs. Determination of acetonitrile and cyanide concentrations in maternal rat blood showed that acetonitrile concentration in the blood increased with exposure concentration for all exposed maternal rats. Detectable amounts of cyanide in the blood were found only in the rats exposed to 1200 ppM acetonitrile ({approximately}2 {mu}g cyanide/g of blood).

  2. Toxicological Outcomes in Rats Exposed to Inhaled Ethanol During Gestation

    Science.gov (United States)

    Recent legislation has encouraged replacing petroleum-based fuels with renewable alternatives including ethanol, which is currently blended with gasoline in the United States at concentrations up to 15%. Efforts to increase the amount of ethanol in gasoline have prompted concerns...

  3. Genotoxicity and subchronic toxicity evaluation of dried Euglena gracilis ATCC PTA-123017.

    Science.gov (United States)

    Simon, Ryan R; Vo, Trung D; Levine, Robert

    2016-10-01

    Euglena gracilis is a microalga capable of synthesizing various nutrients of interest in human and animal nutrition. When cultivated aerobically in the dark, Euglena synthesize paramylon, a storage polysaccharide comprised of high molecular weight beta-1,3-D-glucose polymers organized in cytoplasmic granules. Beta-glucans have been shown to have immune modulation effects, including anti-microbial, anti-tumor, and anti-oxidant properties, and metabolic effects, such as regulation of cholesterol and blood sugar levels. Preparations of E. gracilis and paramylon may therefore have potential utility as functional food ingredients for human and animal nutrition. A battery of toxicological studies was conducted on a dried preparation of E. gracilis and paramylon to support their safe food use. The dried alga was not genotoxic in a bacterial reverse mutation test and mammalian micronucleus test. In the subchronic toxicity study, rats were provided E. gracilis in the diet at levels of 0, 12,500, 25,000 or 50,000 ppm. Paramylon was provided at a concentration of 50,000 ppm. No effects that could be attributable to treatment were observed in clinical observations, body weight, food consumption, ophthalmology, hematology and clinical chemistry, urinalysis, and macroscopic and microscopic findings. A NOAEL of 50,000 ppm in the diet was determined for both ingredients. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Inhalant allergies in children.

    Science.gov (United States)

    Mims, James W; Veling, Maria C

    2011-06-01

    Children with chronic or recurrent upper respiratory inflammatory disease (rhinitis) should be considered for inhalant allergies. Risk factors for inhalant allergies in children include a first-degree relative with allergies, food allergy in infancy, and atopic dermatitis. Although inhalant allergies are rare in infancy, inhalant allergies are common in older children and impair quality of life and productivity. Differentiating between viral and allergic rhinitis can be challenging in children, but the child's age, history, and risk factors can provide helpful information. Allergic rhinitis is a risk factor for asthma, and if one is present, medical consideration of the other is warranted. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Inhalant Abuse and Dextromethorphan.

    Science.gov (United States)

    Storck, Michael; Black, Laura; Liddell, Morgan

    2016-07-01

    Inhalant abuse is the intentional inhalation of a volatile substance for the purpose of achieving an altered mental state. As an important, yet underrecognized form of substance abuse, inhalant abuse crosses all demographic, ethnic, and socioeconomic boundaries, causing significant morbidity and mortality in school-aged and older children. This review presents current perspectives on epidemiology, detection, and clinical challenges of inhalant abuse and offers advice regarding the medical and mental health providers' roles in the prevention and management of this substance abuse problem. Also discussed is the misuse of a specific "over-the-counter" dissociative, dextromethorphan. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Impact of acute and subchronic inhalation exposure to PbO nanoparticles on mice

    Czech Academy of Sciences Publication Activity Database

    Lebedová, J.; Nováková, Z.; Večeřa, Zbyněk; Buchtová, Marcela; Dumková, J.; Dočekal, Bohumil; Bláhová, L.; Mikuška, Pavel; Míšek, Ivan; Hampl, A.; Hilsherová, K.

    2018-01-01

    Roč. 12, č. 4 (2018), s. 290-304 ISSN 1743-5390 R&D Projects: GA ČR(CZ) GAP503/11/2315; GA ČR(CZ) GBP503/12/G147 Institutional support: RVO:68081715 Keywords : nanoparticles * oxidative stress * tissue damage Subject RIV: CB - Analytical Chemistry, Separation OBOR OECD: Analytical chemistry Impact factor: 6.428, year: 2016

  7. Agenda of behavioral toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, B

    1978-01-01

    The author describes behavioral toxicology as a new discipline and contrasts it to the fields of physics and pharmacology. Several questions are raised and discussed concerning the field of behavioral toxicology. Some of these questions are: (1) how is an adverse behavioral effect recognized; (2) how can the non-specific be specified; (3) are standardized test batteries feasible. The problem of chronic intake is discussed as well as drawing information from other related disciplines such as neurochemistry, neuropathology and neurophysiology. The author concludes with several statements concerning new directions in the discipline of behavioral toxicology.

  8. Toxicological benchmarks for wildlife: 1994 Revision

    International Nuclear Information System (INIS)

    Opresko, D.M.; Sample, B.E.; Suter, G.W. II.

    1994-09-01

    The process by which ecological risks of environmental contaminants are evaluated is two-tiered. The first tier is a screening assessment where concentrations of contaminants in the environment are compared to toxicological benchmarks which represent concentrations of chemicals in environmental media (water, sediment, soil, food, etc.) that are presumed to be nonhazardous to the surrounding biota. The second tier is a baseline ecological risk assessment where toxicological benchmarks are one of several lines of evidence used to support or refute the presence of ecological effects. The report presents toxicological benchmarks for assessment of effects of 76 chemicals on 8 representative mammalian wildlife species and 31 chemicals on 9 avian wildlife species. The chemicals are some of those that occur at United States Department of Energy waste sites; the wildlife species were chosen because they are widely distributed and provide a representative range of body sizes and diets. Further descriptions of the chosen wildlife species and chemicals are provided in the report. The benchmarks presented in this report represent values believed to be nonhazardous for the listed wildlife species. These benchmarks only consider contaminant exposure through oral ingestion of contaminated media; exposure through inhalation or direct dermal exposure are not considered in this report

  9. Toxicological benchmarks for wildlife: 1994 Revision

    Energy Technology Data Exchange (ETDEWEB)

    Opresko, D.M.; Sample, B.E.; Suter, G.W. II

    1994-09-01

    The process by which ecological risks of environmental contaminants are evaluated is two-tiered. The first tier is a screening assessment where concentrations of contaminants in the environment are compared to toxicological benchmarks which represent concentrations of chemicals in environmental media (water, sediment, soil, food, etc.) that are presumed to be nonhazardous to the surrounding biota. The second tier is a baseline ecological risk assessment where toxicological benchmarks are one of several lines of evidence used to support or refute the presence of ecological effects. The report presents toxicological benchmarks for assessment of effects of 76 chemicals on 8 representative mammalian wildlife species and 31 chemicals on 9 avian wildlife species. The chemicals are some of those that occur at United States Department of Energy waste sites; the wildlife species were chosen because they are widely distributed and provide a representative range of body sizes and diets. Further descriptions of the chosen wildlife species and chemicals are provided in the report. The benchmarks presented in this report represent values believed to be nonhazardous for the listed wildlife species. These benchmarks only consider contaminant exposure through oral ingestion of contaminated media; exposure through inhalation or direct dermal exposure are not considered in this report.

  10. Objective measurement of inhaler inhalation flow profile using acoustic methods

    Energy Technology Data Exchange (ETDEWEB)

    Lacalle, H.; Taylor, T.E.; Marco, S.; Reilly, R.B.

    2016-07-01

    Patients with asthma and chronic obstructive pulmonary diseases (COPD) are mostly treated with inhalers that deliver medication directly to their airways. Drug delivery from dry powder inhalers (DPIs) is very much reliant on the inhalation manoeuvre, specifically the peak inspiratory flow rate (PIFR), inspiratory capacity (IC) and inhalation rise time (IRT) of the inhalation. It has been widely reported that patients may not follow correct inhalation technique while using their inhaler. In this study, a novel acoustic method is proposed to accurately estimate inhalation flow profile using only one inhalation recording for calibration. An Ellipta DPI was placed inside an airtight container with a spirometer connected in order to measure inhalation flow parameters. An acoustic recording device (Inhaler Compliance Assessment (INCA)) was also attached to the DPI. Inhalation audio and flow signals were recorded simultaneously. The data were collected from 20 healthy subjects while performing inhaler inhalations at a range of inspiratory flow rates. A power law regression model was computed to obtain the relationship between the acoustic envelope of the inhalation and flow profile of each recording. Each model was tested on the remaining audio signals to estimate flow profile. The average estimation error was found to be 10.5±0.3% for estimating flow profile from audio signals. Inhalation flow profile parameters (PIFR, IC and IRT) could then be measured from the estimated flow profile with high accuracy giving information on user inhalation technique. This method may assist in improving patient inhaler adherence and overall disease control. (Author)

  11. Metabonomics and toxicology.

    Science.gov (United States)

    Zhao, Liang; Hartung, Thomas

    2015-01-01

    Being an emerging field of "omics" research, metabonomics has been increasingly used in toxicological studies mostly because this technology has the ability to provide more detailed information to elucidate mechanism of toxicity. As an interdisciplinary field of science, metabonomics combines analytical chemistry, bioinformatics, statistics, and biochemistry. When applied to toxicology, metabonomics also includes aspects of patho-biochemistry, systems biology, and molecular diagnostics. During a toxicological study, the metabolic changes over time and dose after chemical treatment can be monitored. Therefore, the most important use of this emerging technology is the identification of signatures of toxicity-patterns of metabolic changes predictive of a hazard manifestation. This chapter summarizes the current state of metabonomics technology and its applications in various areas of toxicological studies.

  12. Downloadable Computational Toxicology Data

    Science.gov (United States)

    EPA’s computational toxicology research generates data that investigates the potential harm, or hazard of a chemical, the degree of exposure to chemicals as well as the unique chemical characteristics. This data is publicly available here.

  13. Occupational medicine and toxicology

    Directory of Open Access Journals (Sweden)

    Fischer Axel

    2006-02-01

    Full Text Available Abstract This editorial is to announce the Journal of Occupational Medicine and Toxicology, a new Open Access, peer-reviewed, online journal published by BioMed Central. Occupational medicine and toxicology belong to the most wide ranging disciplines of all medical specialties. The field is devoted to the diagnosis, prevention, management and scientific analysis of diseases from the fields of occupational and environmental medicine and toxicology. It also covers the promotion of occupational and environmental health. The complexity of modern industrial processes has dramatically changed over the past years and today's areas include effects of atmospheric pollution, carcinogenesis, biological monitoring, ergonomics, epidemiology, product safety and health promotion. We hope that the launch of the Journal of Occupational Medicine and Toxicology will aid in the advance of these important areas of research bringing together multi-disciplinary research findings.

  14. Progress in computational toxicology.

    Science.gov (United States)

    Ekins, Sean

    2014-01-01

    Computational methods have been widely applied to toxicology across pharmaceutical, consumer product and environmental fields over the past decade. Progress in computational toxicology is now reviewed. A literature review was performed on computational models for hepatotoxicity (e.g. for drug-induced liver injury (DILI)), cardiotoxicity, renal toxicity and genotoxicity. In addition various publications have been highlighted that use machine learning methods. Several computational toxicology model datasets from past publications were used to compare Bayesian and Support Vector Machine (SVM) learning methods. The increasing amounts of data for defined toxicology endpoints have enabled machine learning models that have been increasingly used for predictions. It is shown that across many different models Bayesian and SVM perform similarly based on cross validation data. Considerable progress has been made in computational toxicology in a decade in both model development and availability of larger scale or 'big data' models. The future efforts in toxicology data generation will likely provide us with hundreds of thousands of compounds that are readily accessible for machine learning models. These models will cover relevant chemistry space for pharmaceutical, consumer product and environmental applications. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. In silico toxicology protocols.

    Science.gov (United States)

    Myatt, Glenn J; Ahlberg, Ernst; Akahori, Yumi; Allen, David; Amberg, Alexander; Anger, Lennart T; Aptula, Aynur; Auerbach, Scott; Beilke, Lisa; Bellion, Phillip; Benigni, Romualdo; Bercu, Joel; Booth, Ewan D; Bower, Dave; Brigo, Alessandro; Burden, Natalie; Cammerer, Zoryana; Cronin, Mark T D; Cross, Kevin P; Custer, Laura; Dettwiler, Magdalena; Dobo, Krista; Ford, Kevin A; Fortin, Marie C; Gad-McDonald, Samantha E; Gellatly, Nichola; Gervais, Véronique; Glover, Kyle P; Glowienke, Susanne; Van Gompel, Jacky; Gutsell, Steve; Hardy, Barry; Harvey, James S; Hillegass, Jedd; Honma, Masamitsu; Hsieh, Jui-Hua; Hsu, Chia-Wen; Hughes, Kathy; Johnson, Candice; Jolly, Robert; Jones, David; Kemper, Ray; Kenyon, Michelle O; Kim, Marlene T; Kruhlak, Naomi L; Kulkarni, Sunil A; Kümmerer, Klaus; Leavitt, Penny; Majer, Bernhard; Masten, Scott; Miller, Scott; Moser, Janet; Mumtaz, Moiz; Muster, Wolfgang; Neilson, Louise; Oprea, Tudor I; Patlewicz, Grace; Paulino, Alexandre; Lo Piparo, Elena; Powley, Mark; Quigley, Donald P; Reddy, M Vijayaraj; Richarz, Andrea-Nicole; Ruiz, Patricia; Schilter, Benoit; Serafimova, Rositsa; Simpson, Wendy; Stavitskaya, Lidiya; Stidl, Reinhard; Suarez-Rodriguez, Diana; Szabo, David T; Teasdale, Andrew; Trejo-Martin, Alejandra; Valentin, Jean-Pierre; Vuorinen, Anna; Wall, Brian A; Watts, Pete; White, Angela T; Wichard, Joerg; Witt, Kristine L; Woolley, Adam; Woolley, David; Zwickl, Craig; Hasselgren, Catrin

    2018-04-17

    The present publication surveys several applications of in silico (i.e., computational) toxicology approaches across different industries and institutions. It highlights the need to develop standardized protocols when conducting toxicity-related predictions. This contribution articulates the information needed for protocols to support in silico predictions for major toxicological endpoints of concern (e.g., genetic toxicity, carcinogenicity, acute toxicity, reproductive toxicity, developmental toxicity) across several industries and regulatory bodies. Such novel in silico toxicology (IST) protocols, when fully developed and implemented, will ensure in silico toxicological assessments are performed and evaluated in a consistent, reproducible, and well-documented manner across industries and regulatory bodies to support wider uptake and acceptance of the approaches. The development of IST protocols is an initiative developed through a collaboration among an international consortium to reflect the state-of-the-art in in silico toxicology for hazard identification and characterization. A general outline for describing the development of such protocols is included and it is based on in silico predictions and/or available experimental data for a defined series of relevant toxicological effects or mechanisms. The publication presents a novel approach for determining the reliability of in silico predictions alongside experimental data. In addition, we discuss how to determine the level of confidence in the assessment based on the relevance and reliability of the information. Copyright © 2018. Published by Elsevier Inc.

  16. Comparative toxicological studies on the effects of internal exposures

    International Nuclear Information System (INIS)

    Oghiso, Yoichi; Fukuda, Satoshi; Iida, Haruzo; Yamada, Yuji; Kubota, Yoshihisa; Matsuoka, Osamu

    1989-01-01

    In order to study the toxicological mechanism of transuranic elements, such as plutonium, involved in the induction of pulmonary fibrosis, toxic effects of several inhaled dusts and mineral particles were examined in rats. Pulmonary alveolar macrophage (PAM) was responsible for retention and behavior of inhaled asbestos fibers or silica particles and their transfer to the lymph nodes. PAM exhibited prominent phagocytosis of particles, followed by a significant release of lactic dehydrogenase and beta-glucuronidase. Multinucleated or Ia-positive PAM was frequently observed in rats presenting with pulmonary fibrosis. Pulmonary fibrosis that was induced by inhaled asbestos or silica particles was associated with significant production and release of cytokines. This indicated a close correlation with inflammatory or proliferating responses of fibroblasts and lymphocytes. Such reactions observed in PAM depended on toxicity of particles involved in phagocytosis (i.e., the ability of particles to induce pulmonary fibrosis), suggesting heterogeneity in the population of PAM. (Namekawa, K)

  17. Aspergillus fumigatus viability drives allergic responses to inhaled conidia.

    Science.gov (United States)

    Nayak, Ajay P; Croston, Tara L; Lemons, Angela R; Goldsmith, W T; Marshall, Nikki B; Kashon, Michael L; Germolec, Dori R; Beezhold, Donald H; Green, Brett J

    2018-04-13

    Aspergillus fumigatus induced allergic airway disease has been shown to involve conidial germination in vivo but the immunological mechanisms remain uncharacterized. A subchronic murine exposure model was used to examine the immunological mediators that are regulated in response to either culturable or non-culturable A. fumigatus conidia. Female B6C3F1/N mice were repeatedly dosed via inhalation with 1 x 105 viable or heat inactivated conidia (HIC), twice a week for 13 weeks (26 exposures). Control mice inhaled HEPA-filtered air. The influence of A. fumigatus conidial germination on the pulmonary immunopathological outcomes was evaluated by flow cytometry analysis of cellular infiltration in the airways, assessment of lung mRNA expression, and quantitative proteomics and histopathology of whole lung tissue. Repeated inhalation of viable conidia, but not HIC, resulted in allergic inflammation marked by vascular remodeling, extensive eosinophilia, and accumulation of alternatively activated macrophages (AAMs) in the murine airways. More specifically, mice that inhaled viable conidia resulted in a mixed TH1 and TH2 (IL-13) cytokine response. Recruitment of eosinophils corresponded with increased Ccl11 transcripts. Furthermore, genes associated with M2 or alternatively activated macrophage polarization (e.g. Arg1, Chil3 and Retnla) were significantly upregulated in viable A. fumigatus exposed mice. In mice inhaling HIC, CD4+ T cells expressing IFN-γ (TH1) dominated the lymphocytic infiltration. Quantitative proteomics of the lung revealed metabolic reprogramming accompanied by mitochondrial dysfunction and endoplasmic reticulum stress stimulated by oxidative stress from repetitive microbial insult. Our studies demonstrate that A. fumigatus conidial viability in vivo is critical to the immunopathological presentation of chronic fungal allergic disease. Copyright © 2018. Published by Elsevier Inc.

  18. Subchronic exposure to sublethal dose of imidacloprid changes electrophysiological properties and expression pattern of nicotinic acetylcholine receptor subtypes in insect neurosecretory cells.

    Science.gov (United States)

    Benzidane, Yassine; Goven, Delphine; Abd-Ella, Aly Ahmed; Deshayes, Caroline; Lapied, Bruno; Raymond, Valérie

    2017-09-01

    Neonicotinoids are the most important class of insecticides used in agriculture over the last decade. They act as selective agonists of insect nicotinic acetylcholine receptors (nAChRs). The emergence of insect resistance to these insecticides is one of the major problems, which limit the use of neonicotinoids. The aim of our study is to better understand physiological changes appearing after subchronic exposure to sublethal doses of insecticide using complementary approaches that include toxicology, electrophysiology, molecular biology and calcium imaging. We used cockroach neurosecretory cells identified as dorsal unpaired median (DUM) neurons, known to express two α-bungarotoxin-insensitive (α-bgt-insensitive) nAChR subtypes, nAChR1 and nAChR2, which differ in their sensitivity to imidacloprid. Although nAChR1 is sensitive to imidacloprid, nAChR2 is insensitive to this insecticide. In this study, we demonstrate that subchronic exposure to sublethal dose of imidacloprid differentially changes physiological and molecular properties of nAChR1 and nAChR2. Our findings reported that this treatment decreased the sensitivity of nAChR1 to imidacloprid, reduced current density flowing through this nAChR subtype but did not affect its subunit composition (α3, α8 and β1). Subchronic exposure to sublethal dose of imidacloprid also affected nAChR2 functions. However, these effects were different from those reported on nAChR1. We observed changes in nAChR2 conformational state, which could be related to modification of the subunit composition (α1, α2 and β1). Finally, the subchronic exposure affecting both nAChR1 and nAChR2 seemed to be linked to the elevation of the steady-state resting intracellular calcium level. In conclusion, under subchronic exposure to sublethal dose of imidacloprid, cockroaches are capable of triggering adaptive mechanisms by reducing the participation of imidacloprid-sensitive nAChR1 and by optimizing functional properties of nAChR2, which is

  19. Inhalants in Peru.

    Science.gov (United States)

    Lerner, R; Ferrando, D

    1995-01-01

    In Peru, the prevalence and consequences of inhalant abuse appear to be low in the general population and high among marginalized children. Inhalant use ranks third in lifetime prevalence after alcohol and tobacco. Most of the use appears to be infrequent. Among marginalized children, that is, children working in the streets but living at home or children living in the street, the problem of inhalant abuse is a serious problem. Among children working in the streets but living at home, the lifetime prevalence rate for inhalant abuse is high, ranging from 15 to 45 percent depending on the study being cited. For children living in the streets, the use of inhalant is even more severe. As mentioned earlier in this chapter, most of these street children use inhalants on a daily basis. The lack of research on the problem of inhalant abuse is a serious impediment to development of intervention programs and strategies to address this problem in Peru. Epidemiologic and ethnographic research on the nature and extent of inhalant abuse are obvious prerequisites to targeted treatment and preventive intervention programs. The urgent need for current and valid data is underscored by the unique vulnerability of the youthful population at risk and the undisputed harm that results from chronic abuse of inhalants. Nonetheless, it is important to mention several programs that work with street children. Some, such as the Information and Education Center for the Prevention of Drug Abuse, Generation, and Centro Integracion de Menores en Abandono have shelters where street children are offered transition to a less marginal lifestyle. Teams of street educators provide the children with practical solutions and gain their confidence, as well as offer them alternative socialization experiences to help them survive the streets and avoid the often repressive and counterproductive environments typical of many institutions. Most of the children who go through these programs tend to abandon

  20. Whole-body nanoparticle aerosol inhalation exposures.

    Science.gov (United States)

    Yi, Jinghai; Chen, Bean T; Schwegler-Berry, Diane; Frazer, Dave; Castranova, Vince; McBride, Carroll; Knuckles, Travis L; Stapleton, Phoebe A; Minarchick, Valerie C; Nurkiewicz, Timothy R

    2013-05-07

    Inhalation is the most likely exposure route for individuals working with aerosolizable engineered nano-materials (ENM). To properly perform nanoparticle inhalation toxicology studies, the aerosols in a chamber housing the experimental animals must have: 1) a steady concentration maintained at a desired level for the entire exposure period; 2) a homogenous composition free of contaminants; and 3) a stable size distribution with a geometric mean diameter generation of aerosols containing nanoparticles is quite challenging because nanoparticles easily agglomerate. This is largely due to very strong inter-particle forces and the formation of large fractal structures in tens or hundreds of microns in size (6), which are difficult to be broken up. Several common aerosol generators, including nebulizers, fluidized beds, Venturi aspirators and the Wright dust feed, were tested; however, none were able to produce nanoparticle aerosols which satisfy all criteria (5). A whole-body nanoparticle aerosol inhalation exposure system was fabricated, validated and utilized for nano-TiO2 inhalation toxicology studies. Critical components: 1) novel nano-TiO2 aerosol generator; 2) 0.5 m(3) whole-body inhalation exposure chamber; and 3) monitor and control system. Nano-TiO2 aerosols generated from bulk dry nano-TiO2 powders (primary diameter of 21 nm, bulk density of 3.8 g/cm(3)) were delivered into the exposure chamber at a flow rate of 90 LPM (10.8 air changes/hr). Particle size distribution and mass concentration profiles were measured continuously with a scanning mobility particle sizer (SMPS), and an electric low pressure impactor (ELPI). The aerosol mass concentration (C) was verified gravimetrically (mg/m(3)). The mass (M) of the collected particles was determined as M = (Mpost-Mpre), where Mpre and Mpost are masses of the filter before and after sampling (mg). The mass concentration was calculated as C = M/(Q*t), where Q is sampling flowrate (m(3)/min), and t is the sampling

  1. A whiff of death: fatal volatile solvent inhalation abuse.

    Science.gov (United States)

    Steffee, C H; Davis, G J; Nicol, K K

    1996-09-01

    Inhalation abuse of volatile solvents, previously known generically as "glue sniffing," is typically pursued by adolescents. A wide range of legal, easily obtained products containing volatile substances are available for abuse. We report two illustrative cases of fatal volatile substance abuse: gasoline sniffing in a 20-year-old man and aerosol propellant gas inhalation (aerosol air freshener) in a 16-year-old girl with underlying reactive airway disease. Although the ratio of deaths to nonfatal inhalation escapades is extremely low, volatile solvent abuse carries the risk of sudden death due to cardiac arrest after a dysrhythmia or vasovagal event, central nervous system respiratory depression, hypoxia and hypercapnia due to the techniques of inhalation, and other mechanisms. Investigation of the patient's substance abuse history, examination of the scene of death, and special toxicologic analyses are critical to identifying volatile substance inhalation abuse as the cause of death because anatomic autopsy findings will typically be nonspecific. Above all, physicians must suspect the diagnosis of volatile substance inhalation abuse, especially in any case of sudden death involving an otherwise healthy young person.

  2. Exposure to acrolein by inhalation causes platelet activation

    International Nuclear Information System (INIS)

    Sithu, Srinivas D.; Srivastava, Sanjay; Siddiqui, Maqsood A.; Vladykovskaya, Elena; Riggs, Daniel W.; Conklin, Daniel J.; Haberzettl, Petra; O'Toole, Timothy E.; Bhatnagar, Aruni; D'Souza, Stanley E.

    2010-01-01

    Acrolein is a common air pollutant that is present in high concentrations in wood, cotton, and tobacco smoke, automobile exhaust and industrial waste and emissions. Exposure to acrolein containing environmental pollutants such as tobacco smoke and automobile exhaust has been linked to the activation of the coagulation and hemostasis pathways and thereby to the predisposition of thrombotic events in human. To examine the effects of acrolein on platelets, adult male C57Bl/6 mice were subjected acute (5 ppm for 6 h) or sub-chronic (1 ppm, 6 h/day for 4 days) acrolein inhalation exposures. The acute exposure to acrolein did not cause pulmonary inflammation and oxidative stress, dyslipidemia or induce liver damage or muscle injury. Platelet GSH levels in acrolein-exposed mice were comparable to controls, but acrolein-exposure increased the abundance of protein-acrolein adducts in platelets. Platelets isolated from mice, exposed to both acute and sub-chronic acrolein levels, showed increased ADP-induced platelet aggregation. Exposure to acrolein also led to an increase in the indices of platelet activation such as the formation of platelet-leukocyte aggregates in the blood, plasma PF4 levels, and increased platelet-fibrinogen binding. The bleeding time was decreased in acrolein exposed mice. Plasma levels of PF4 were also increased in mice exposed to environmental tobacco smoke. Similar to inhalation exposure, acrolein feeding to mice also increased platelet activation and established a pro-thrombotic state in mice. Together, our data suggest that acrolein is an important contributing factor to the pro-thrombotic risk in human exposure to pollutants such as tobacco smoke or automobile exhaust, or through dietary consumption.

  3. Exposure to acrolein by inhalation causes platelet activation

    Energy Technology Data Exchange (ETDEWEB)

    Sithu, Srinivas D [Department of Physiology and Biophysics, University of Louisville, Louisville, KY 40202 (United States); Diabetes and Obesity Center, University of Louisville, Louisville, KY 40202 (United States); Srivastava, Sanjay; Siddiqui, Maqsood A; Vladykovskaya, Elena; Riggs, Daniel W; Conklin, Daniel J; Haberzettl, Petra; O' Toole, Timothy E; Bhatnagar, Aruni [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40202 (United States); D' Souza, Stanley E., E-mail: sedsou01@louisville.ed [Department of Physiology and Biophysics, University of Louisville, Louisville, KY 40202 (United States)

    2010-10-15

    Acrolein is a common air pollutant that is present in high concentrations in wood, cotton, and tobacco smoke, automobile exhaust and industrial waste and emissions. Exposure to acrolein containing environmental pollutants such as tobacco smoke and automobile exhaust has been linked to the activation of the coagulation and hemostasis pathways and thereby to the predisposition of thrombotic events in human. To examine the effects of acrolein on platelets, adult male C57Bl/6 mice were subjected acute (5 ppm for 6 h) or sub-chronic (1 ppm, 6 h/day for 4 days) acrolein inhalation exposures. The acute exposure to acrolein did not cause pulmonary inflammation and oxidative stress, dyslipidemia or induce liver damage or muscle injury. Platelet GSH levels in acrolein-exposed mice were comparable to controls, but acrolein-exposure increased the abundance of protein-acrolein adducts in platelets. Platelets isolated from mice, exposed to both acute and sub-chronic acrolein levels, showed increased ADP-induced platelet aggregation. Exposure to acrolein also led to an increase in the indices of platelet activation such as the formation of platelet-leukocyte aggregates in the blood, plasma PF4 levels, and increased platelet-fibrinogen binding. The bleeding time was decreased in acrolein exposed mice. Plasma levels of PF4 were also increased in mice exposed to environmental tobacco smoke. Similar to inhalation exposure, acrolein feeding to mice also increased platelet activation and established a pro-thrombotic state in mice. Together, our data suggest that acrolein is an important contributing factor to the pro-thrombotic risk in human exposure to pollutants such as tobacco smoke or automobile exhaust, or through dietary consumption.

  4. A plastic stabilizer dibutyltin dilaurate induces subchronic neurotoxicity in rats☆

    OpenAIRE

    Jin, Minghua; Song, Peilin; Li, Na; Li, Xuejun; Chen, Jiajun

    2012-01-01

    Dibutyltin dilaurate functions as a stabilizer for polyvinyl chloride. In this study, experimental rats were intragastrically administered 5, 10, or 20 mg/kg dibutyltin dilaurate to model sub-chronic poisoning. After exposure, our results showed the activities of superoxide dismutase and glutathione peroxidase decreased in rat brain tissue, while the malondialdehyde and nitric oxide content, as well as nitric oxide synthase activity in rat brain tissue increased. The cell cycle in the right p...

  5. Sub-chronic lung inflammation after airway exposures to Bacillus thuringiensis biopesticides in mice

    Directory of Open Access Journals (Sweden)

    Barfod Kenneth K

    2010-09-01

    exposures to commercial Bt based biopesticides can induce sub-chronic lung inflammation in mice, which may be the first step in the development of chronic lung diseases. Inhalation of Bt aerosols does not induce airway irritation, which could explain why workers may be less inclined to use a filter mask during the application process, and are thereby less protected from exposure to Bt spores.

  6. Acute and sub-chronic toxicity studies of honokiol microemulsion.

    Science.gov (United States)

    Zhang, Qianqian; Li, Jianguo; Zhang, Wei; An, Quan; Wen, Jianhua; Wang, Aiping; Jin, Hongtao; Chen, Shizhong

    2015-04-01

    The purpose of this study was to investigate the acute and sub-chronic toxicity of honokiol microemulsion. In the acute toxicity tests, the mice were intravenously injected graded doses of honokiol microemulsion and were observed for toxic symptoms and mortality daily for 14 days. In the sub-chronic toxicity study, rats were injected honokiol microemulsion at doses of 100, 500, 2500 μg/kg body weight (BW) for 30 days. After 30 days treatment and 14 days recovery, the rats were sacrificed for hematological, biochemical and histological examination. In the acute toxicity tests, the estimated median lethal dosage (LD50) was 50.5mg/kg body weight in mice. In the sub-chronic toxicity tests, the non-toxic reaction dose was 500 μg/kg body weight. In each treatment group, degeneration or/and necrosis in vascular endothelial cells and structure change of vessel wall can be observed in the injection site (cauda vein) of a few animals while there were no changes in the vessels of other organs. The overall findings of this study indicate that the honokiol microemulsion is non-toxic up to 500 μg/kg body weight, and it has irritation to the vascular of the injection site which should be paid attention to in clinical medication. Copyright © 2015. Published by Elsevier Inc.

  7. Safety evaluation of β-glucanase derived from Trichoderma reesei: Summary of toxicological data

    NARCIS (Netherlands)

    Coenen, T.M.M.; Schoenmakers, A.C.M.; Verhagen, H.

    1995-01-01

    Barlican, a β-glucanase enzyme obtained from Trichoderma reesei, was produced by a fermentation process and subjected to a series of toxicological tests to document its safety for use as a feed additive. The enzyme product was examined for general oral toxicity, inhalation toxicity, irritation to

  8. Aerospace Toxicology and Microbiology

    Science.gov (United States)

    James, John T.; Parmet, A. J.; Pierson, Duane L.

    2007-01-01

    Toxicology dates to the very earliest history of humanity with various poisons and venom being recognized as a method of hunting or waging war with the earliest documentation in the Evers papyrus (circa 1500 BCE). The Greeks identified specific poisons such as hemlock, a method of state execution, and the Greek word toxos (arrow) became the root of our modern science. The first scientific approach to the understanding of poisons and toxicology was the work during the late middle ages of Paracelsus. He formulated what were then revolutionary views that a specific toxic agent or "toxicon" caused specific dose-related effects. His principles have established the basis of modern pharmacology and toxicology. In 1700, Bernardo Ramazzini published the book De Morbis Artificum Diatriba (The Diseases of Workers) describing specific illnesses associated with certain labor, particularly metal workers exposed to mercury, lead, arsenic, and rock dust. Modern toxicology dates from development of the modern industrial chemical processes, the earliest involving an analytical method for arsenic by Marsh in 1836. Industrial organic chemicals were synthesized in the late 1800 s along with anesthetics and disinfectants. In 1908, Hamilton began the long study of occupational toxicology issues, and by WW I the scientific use of toxicants saw Haber creating war gases and defining time-dosage relationships that are used even today.

  9. Animal-free toxicology

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E

    2013-01-01

    Human data on exposure and adverse effects are the most appropriate for human risk assessment, and modern toxicology focuses on human pathway analysis and the development of human biomarkers. Human biomonitoring and human placental transport studies provide necessary information for human risk...... assessment, in accordance with the legislation on chemical, medicine and food safety. Toxicology studies based on human mechanistic and exposure information can replace animal studies. These animal-free approaches can be further supplemented by new in silico methods and chemical structure......-activity relationships. The inclusion of replacement expertise in the international Three Rs centres, the ongoing exploration of alternatives to animal research, and the improvement of conditions for research animals, all imply the beginning of a paradigm shift in toxicology research toward the use of human data....

  10. Olodaterol Oral Inhalation

    Science.gov (United States)

    ... in a class of medications called long-acting beta-agonists (LABAs). It works by relaxing and opening ... the inhaler upright with the yellow cap closed. Turn the clear base in the direction of the ...

  11. Pirbuterol Acetate Oral Inhalation

    Science.gov (United States)

    ... Pirbuterol is in a class of medications called beta-agonist bronchodilators. It works by relaxing and opening ... cleaning. Once a week, remove the mouthpiece cover, turn the inhaler upside down and wipe the mouthpiece ...

  12. Cromolyn Oral Inhalation

    Science.gov (United States)

    ... your doctor.Cromolyn oral inhalation helps to prevent asthma attacks (sudden episodes of shortness of breath, wheezing, and coughing) but will not stop an asthma attack that has already started. Your doctor will prescribe ...

  13. Ipratropium Oral Inhalation

    Science.gov (United States)

    ... with the clear end pointing upward. Place the metal canister inside the clear end of the inhaler. ... do not discard it in an incinerator or fire.Unneeded medications should be disposed of in special ...

  14. Nicotine Oral Inhalation

    Science.gov (United States)

    ... with a smoking cessation program, which may include support groups, counseling, or specific behavioral change techniques. Nicotine inhalation ... and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or ...

  15. Shuttle Lesson Learned - Toxicology

    Science.gov (United States)

    James, John T.

    2010-01-01

    This is a script for a video about toxicology and the space shuttle. The first segment is deals with dust in the space vehicle. The next segment will be about archival samples. Then we'll look at real time on-board analyzers that give us a lot of capability in terms of monitoring for combustion products and the ability to monitor volatile organics on the station. Finally we will look at other issues that are about setting limits and dealing with ground based lessons that pertain to toxicology.

  16. Radioactive gas inhalator

    International Nuclear Information System (INIS)

    LeMon, D.E.

    1975-01-01

    An ''inhalator'', or more particularly an apparatus for permitting a patient to inhale a radioactive gas in order to provide a diagnostic test of the patient's lung area, is described. The disclosed apparatus provides a simple, trouble-free mechanism for achieving this result; and, furthermore, provides an improved testing method. Moreover, the disclosed apparatus has the capability of gradually introducing the test condition in a manner that makes it easy for the patient to become acclimated to it. (U.S.)

  17. Toxicología Vegetal

    OpenAIRE

    García Fernández, Antonio Juan

    2010-01-01

    Presentaciones de clase de los temas de Toxicología Vegetal de la licenciatura de Veterinaria de la Universidad de Murcia del curso 2011/12. Presentaciones de Toxicología Vegetal de la asignatura de Toxicología de la Licenciatura de Veterinaria del curso 2011/12

  18. Air pollution & the brain: Subchronic diesel exhaust exposure causes neuroinflammation and elevates early markers of neurodegenerative disease.

    Science.gov (United States)

    Levesque, Shannon; Surace, Michael J; McDonald, Jacob; Block, Michelle L

    2011-08-24

    Increasing evidence links diverse forms of air pollution to neuroinflammation and neuropathology in both human and animal models, but the effects of long-term exposures are poorly understood. We explored the central nervous system consequences of subchronic exposure to diesel exhaust (DE) and addressed the minimum levels necessary to elicit neuroinflammation and markers of early neuropathology. Male Fischer 344 rats were exposed to DE (992, 311, 100, 35 and 0 μg PM/m³) by inhalation over 6 months. DE exposure resulted in elevated levels of TNFα at high concentrations in all regions tested, with the exception of the cerebellum. The midbrain region was the most sensitive, where exposures as low as 100 μg PM/m³ significantly increased brain TNFα levels. However, this sensitivity to DE was not conferred to all markers of neuroinflammation, as the midbrain showed no increase in IL-6 expression at any concentration tested, an increase in IL-1β at only high concentrations, and a decrease in MIP-1α expression, supporting that compensatory mechanisms may occur with subchronic exposure. Aβ42 levels were the highest in the frontal lobe of mice exposed to 992 μg PM/m³ and tau [pS199] levels were elevated at the higher DE concentrations (992 and 311 μg PM/m³) in both the temporal lobe and frontal lobe, indicating that proteins linked to preclinical Alzheimer's disease were affected. α Synuclein levels were elevated in the midbrain in response to the 992 μg PM/m³ exposure, supporting that air pollution may be associated with early Parkinson's disease-like pathology. Together, the data support that the midbrain may be more sensitive to the neuroinflammatory effects of subchronic air pollution exposure. However, the DE-induced elevation of proteins associated with neurodegenerative diseases was limited to only the higher exposures, suggesting that air pollution-induced neuroinflammation may precede preclinical markers of neurodegenerative disease in the midbrain.

  19. Air pollution & the brain: Subchronic diesel exhaust exposure causes neuroinflammation and elevates early markers of neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    McDonald Jacob

    2011-08-01

    Full Text Available Abstract Background Increasing evidence links diverse forms of air pollution to neuroinflammation and neuropathology in both human and animal models, but the effects of long-term exposures are poorly understood. Objective We explored the central nervous system consequences of subchronic exposure to diesel exhaust (DE and addressed the minimum levels necessary to elicit neuroinflammation and markers of early neuropathology. Methods Male Fischer 344 rats were exposed to DE (992, 311, 100, 35 and 0 μg PM/m3 by inhalation over 6 months. Results DE exposure resulted in elevated levels of TNFα at high concentrations in all regions tested, with the exception of the cerebellum. The midbrain region was the most sensitive, where exposures as low as 100 μg PM/m3 significantly increased brain TNFα levels. However, this sensitivity to DE was not conferred to all markers of neuroinflammation, as the midbrain showed no increase in IL-6 expression at any concentration tested, an increase in IL-1β at only high concentrations, and a decrease in MIP-1α expression, supporting that compensatory mechanisms may occur with subchronic exposure. Aβ42 levels were the highest in the frontal lobe of mice exposed to 992 μg PM/m3 and tau [pS199] levels were elevated at the higher DE concentrations (992 and 311 μg PM/m3 in both the temporal lobe and frontal lobe, indicating that proteins linked to preclinical Alzheimer's disease were affected. α Synuclein levels were elevated in the midbrain in response to the 992 μg PM/m3 exposure, supporting that air pollution may be associated with early Parkinson's disease-like pathology. Conclusions Together, the data support that the midbrain may be more sensitive to the neuroinflammatory effects of subchronic air pollution exposure. However, the DE-induced elevation of proteins associated with neurodegenerative diseases was limited to only the higher exposures, suggesting that air pollution-induced neuroinflammation may

  20. Toxicological aspects of water

    International Nuclear Information System (INIS)

    Garcia Puertas, P.

    1991-01-01

    Different toxicological aspects of water have been studied, remarking the activity of various chemical substances in the organism. These substances are divided in: trace metals (Sb, As, Cd, Zn, Cu, Cr, Fe, Mn, Hg, Ni, Pb, Se), other contaminants (CN-, polycyclic aromatic hydrocarbons, phenols, pesticides, detergents) and radioactivity. Finally, some considerations on this subject are made [es

  1. Fatal accidental inhalation of brake cleaner aerosols.

    Science.gov (United States)

    Veit, F; Martz, W; Birngruber, C G; Dettmeyer, R B

    2018-04-23

    Brake cleaner liquid is commonly used for cleaning of engines and motor parts. The commercially available products usually contain mainly volatile organic compounds. As a consequence brake cleaner evaporates fast and almost completely from the cleaned surface. This case report presents a fatal accidental inhalation of brake cleaner liquid aerosols due to the attempted cleaning of a boat engine. A 16year old boy was found lifeless in the engine compartment of a boat engine. In close proximity to the body, the police found cleanings wipes soaked with brake cleaner as well as a pump spray bottle filled with brake cleaner. Essentially the autopsy revealed a cerebral oedema with encephalomalacia, no coagulated blood as well as increased blood and tissue fluid content of the lung. Toxicological analysis revealed brake cleaner fluid in the lung, gastric content and heart blood. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Histological changes in lung tissues related with sub-chronic exposure to ambient urban levels of PM2.5 in Córdoba, Argentina

    Science.gov (United States)

    Tavera Busso, Iván; Vera, Anahí; Mateos, Ana Carolina; Amarillo, Ana Carolina; Carreras, Hebe

    2017-10-01

    Concentration of fine particulate matter (PM2.5) is one of the most important environmental parameters to estimate health impacts attributable to air pollution. Despite the fact there are many studies regarding PM2.5 effects on human health, most of them were performed under conditions that do not simulate the natural particles interaction with the organism. In the present paper, we studied the effects of mammals' sub-chronic exposure to PM2.5 on the lower respiratory tract, addressing realistic exposure conditions to normal urban air. Thus, we exposed Wistar rats under controlled settings to the same normal urban air, with and without particles. Next, we analyzed chemical composition of PM2.5 and lungs samples, performed a histologic examination and run the comet assay to assess genotoxic effects. We found a strong agreement between lung tissues and PM2.5 elemental composition suggesting that metals found in lungs came from the particles inhaled. Histological analysis showed a mild to moderate infiltration, with a reduction of alveoli lumen and increment of alveolar macrophages and periodic acid-Schiff (PAS) (+) cells in treated animals. We also observed an increase in the number of nuclei with comets, mostly comets type 3, with a high DNA fragmentation as well. These results provide strong evidence that sub-chronic exposure to low particle levels, even below the 24 h WHO standard, can cause injuries in lungs tissues and DNA damage, as well.

  3. Health effects of subchronic exposure to environmental levels of diesel exhaust.

    Science.gov (United States)

    Reed, M D; Gigliotti, A P; McDonald, J D; Seagrave, J C; Seilkop, S K; Mauderly, J L

    2004-04-01

    Diesel exhaust is a public health concern and contributor to both ambient and occupational air pollution. As part of a general health assessment of multiple anthropogenic source emissions conducted by the National Environmental Respiratory Center (NERC), a series of health assays was conducted on rats and mice exposed to environmentally relevant levels of diesel exhaust. This article summarizes the study design and exposures, and reports findings on several general indicators of toxicity and carcinogenic potential. Diesel exhaust was generated from a commonly used 2000 model 5.9-L, 6-cylinder turbo diesel engine operated on a variable-load heavy-duty test cycle burning national average certification fuel. Animals were exposed to clean air (control) or four dilutions of whole emissions based on particulate matter concentration (30, 100, 300, and 1000 microg/m(3)). Male and female F344 rats and A/J mice were exposed by whole-body inhalation 6 h/day, 7 days/wk, for either 1 wk or 6 mo. Exposures were characterized in detail. Effects of exposure on clinical observations, body and organ weights, serum chemistry, hematology, histopathology, bronchoalveolar lavage, and serum clotting factors were mild. Significant exposure-related effects occurring in both male and female rats included decreases in serum cholesterol and clotting Factor VII and slight increases in serum gamma-glutamyl transferase. Several other responses met screening criteria for significant exposure effects but were not consistent between genders or exposure times and were not corroborated by related parameters. Carcinogenic potential as determined by micronucleated reticulocyte counts and proliferation of adenomas in A/J mice were unaffected by 6 mo of exposure. Parallel studies demonstrated effects on cardiac function and resistance to viral infection; however, the results reported here show few and only modest health hazards from subchronic or shorter exposures to realistic concentrations of

  4. [Subchronic toxicity testing of mold-ripened cheese].

    Science.gov (United States)

    Schoch, U; Lüthy, J; Schlatter, C

    1984-08-01

    The biological effects of known mycotoxins of Penicillium roqueforti or P. camemberti and other still unknown, but potentially toxic metabolites in mould ripened cheese (commercial samples of Blue- and Camembert cheese) were investigated. High amounts of mycelium (equivalents of 100 kg cheese/man and day) were fed to mice in a subchronic feeding trial. The following parameters were determined: development of body weight, organ weights, hematology, blood plasma enzymes. No signs of adverse effects produced by cheese mycotoxins could be detected after 28 days. No still unknown toxic metabolites could be demonstrated. From these results no health hazard from the consumption of mould ripened cheese, even in high amounts, appears to exist.

  5. Inhaled americium dioxide

    International Nuclear Information System (INIS)

    Park, J.F.

    1982-01-01

    This project includes experiments to determine the effects of Zn-DTPA therapy on the retention, translocation and biological effects of inhaled 241 AmO 2 . Beagle dogs that received inhalation exposure to 241 AmO 2 developed leukopenia, clincial chemistry changes associated with hepatocellular damage, and were euthanized due to respiratory insufficiency caused by radiation pneumonitis 120 to 131 days after pulmonary deposition of 22 to 65 μCi 241 Am. Another group of dogs that received inhalation exposure to 241 AmO 2 and were treated daily with Zn-DTPA had initial pulmonary deposition of 19 to 26 μCi 241 Am. These dogs did not develop respiratory insufficiency, and hematologic and clinical chemistry changes were less severe than in the non-DTPA-treated dogs

  6. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... KB] Using a metered dose inhaler (inhaler in mouth) Your browser does not support iframes Using a metered dose inhaler (inhaler in mouth) [PDF – 370 KB] Your browser does not support ...

  7. Subchronic JP-8 jet fuel exposure enhances vulnerability to noise-induced hearing loss in rats.

    Science.gov (United States)

    Fechter, L D; Fisher, J W; Chapman, G D; Mokashi, V P; Ortiz, P A; Reboulet, J E; Stubbs, J E; Lear, A M; McInturf, S M; Prues, S L; Gearhart, C A; Fulton, S; Mattie, D R

    2012-01-01

    Both laboratory and epidemiological studies published over the past two decades have identified the risk of excess hearing loss when specific chemical contaminants are present along with noise. The objective of this study was to evaluate the potency of JP-8 jet fuel to enhance noise-induced hearing loss (NIHL) using inhalation exposure to fuel and simultaneous exposure to either continuous or intermittent noise exposure over a 4-wk exposure period using both male and female Fischer 344 rats. In the initial study, male (n = 5) and female (n = 5) rats received inhalation exposure to JP-8 fuel for 6 h/d, 5 d/wk for 4 wk at concentrations of 200, 750, or 1500 mg/m³. Parallel groups of rats also received nondamaging noise (constant octave band noise at 85 dB(lin)) in combination with the fuel, noise alone (75, 85, or 95 dB), or no exposure to fuel or noise. Significant concentration-related impairment of auditory function measured by distortion product otoacoustic emissions (DPOAE) and compound action potential (CAP) threshold was seen in rats exposed to combined JP-8 plus noise exposure when JP-8 levels of 1500 mg/m³ were presented with trends toward impairment seen with 750 mg/m³ JP-8 + noise. JP-8 alone exerted no significant effect on auditory function. In addition, noise was able to disrupt the DPOAE and increase auditory thresholds only when noise exposure was at 95 dB. In a subsequent study, male (n = 5 per group) and female (n = 5 per group) rats received 1000 mg/m³ JP-8 for 6 h/d, 5 d/wk for 4 wk with and without exposure to 102 dB octave band noise that was present for 15 min out of each hour (total noise duration 90 min). Comparisons were made to rats receiving only noise, and thosereceiving no experimental treatment. Significant impairment of auditory thresholds especially for high-frequency tones was identified in the male rats receiving combined treatment. This study provides a basis for estimating excessive hearing loss under

  8. Murine pulmonary responses after sub-chronic exposure to aluminum oxide-based nanowhiskers

    Directory of Open Access Journals (Sweden)

    Adamcakova-Dodd Andrea

    2012-06-01

    Full Text Available Abstract Background Aluminum oxide-based nanowhiskers (AO nanowhiskers have been used in manufacturing processes as catalyst supports, flame retardants, adsorbents, or in ceramic, metal and plastic composite materials. They are classified as high aspect ratio nanomaterials. Our aim was to assess in vivo toxicity of inhaled AO nanowhisker aerosols. Methods Primary dimensions of AO nanowhiskers specified by manufacturer were 2–4 nm x 2800 nm. The aluminum content found in this nanomaterial was 30% [mixed phase material containing Al(OH3 and AlOOH]. Male mice (C57Bl/6 J were exposed to AO nanowhiskers for 4 hrs/day, 5 days/wk for 2 or 4 wks in a dynamic whole body exposure chamber. The whiskers were aerosolized with an acoustical dry aerosol generator that included a grounded metal elutriator and a venturi aspirator to enhance deagglomeration. Average concentration of aerosol in the chamber was 3.3 ± 0.6 mg/m3 and the mobility diameter was 150 ± 1.6 nm. Both groups of mice (2 or 4 wks exposure were necropsied immediately after the last exposure. Aluminum content in the lung, heart, liver, and spleen was determined. Pulmonary toxicity assessment was performed by evaluation of bronchoalveolar lavage (BAL fluid (enumeration of total and differential cells, total protein, activity of lactate dehydrogenase [LDH] and cytokines, blood (total and differential cell counts, lung histopathology and pulmonary mechanics. Results Following exposure, mean Al content of lungs was 0.25, 8.10 and 15.37 μg/g lung (dry wt respectively for sham, 2 wk and 4 wk exposure groups. The number of total cells and macrophages in BAL fluid was 2-times higher in animals exposed for 2 wks and 6-times higher in mice exposed for 4 wks, compared to shams (p p  Conclusions Sub-chronic inhalation exposures to aluminum-oxide based nanowhiskers induced increased lung macrophages, but no inflammatory or toxic responses were observed.

  9. Veterinary Forensic Toxicology.

    Science.gov (United States)

    Gwaltney-Brant, S M

    2016-09-01

    Veterinary pathologists working in diagnostic laboratories are sometimes presented with cases involving animal poisonings that become the object of criminal or civil litigation. Forensic veterinary toxicology cases can include cases involving animal cruelty (malicious poisoning), regulatory issues (eg, contamination of the food supply), insurance litigation, or poisoning of wildlife. An understanding of the appropriate approach to these types of cases, including proper sample collection, handling, and transport, is essential so that chain of custody rules are followed and proper samples are obtained for toxicological analysis. Consultation with veterinary toxicologists at the diagnostic laboratory that will be processing the samples before, during, and after the forensic necropsy can help to ensure that the analytical tests performed are appropriate for the circumstances and findings surrounding the individual case. © The Author(s) 2016.

  10. Toxicology of inorganic tin

    International Nuclear Information System (INIS)

    Burba, J.V.

    1982-01-01

    Tin(II) or stannous ion as a reducing agent is important in nuclear medicine because it is an essential component and common denominator for many in vivo radiodiagnostic agents, commonly called kits for the preparation of radiopharmaceuticals. This report is intended to alert nuclear medicine community regarding the wide range of biological effects that the stannous ion is capable of producing, and is a review of a large number of selected publications on the toxicological potential of tin(II)

  11. Toxicology of perfluorinated compounds

    Energy Technology Data Exchange (ETDEWEB)

    Stahl, Thorsten [Hessian State Laboratory, Wiesbaden (Germany); Mattern, Daniela; Brunn, Hubertus [Hessian State Laboratory, Giessen (Germany)

    2011-12-15

    Perfluorinated compounds [PFCs] have found a wide use in industrial products and processes and in a vast array of consumer products. PFCs are molecules made up of carbon chains to which fluorine atoms are bound. Due to the strength of the carbon/fluorine bond, the molecules are chemically very stable and are highly resistant to biological degradation; therefore, they belong to a class of compounds that tend to persist in the environment. These compounds can bioaccumulate and also undergo biomagnification. Within the class of PFC chemicals, perfluorooctanoic acid and perfluorosulphonic acid are generally considered reference substances. Meanwhile, PFCs can be detected almost ubiquitously, e.g., in water, plants, different kinds of foodstuffs, in animals such as fish, birds, in mammals, as well as in human breast milk and blood. PFCs are proposed as a new class of 'persistent organic pollutants'. Numerous publications allude to the negative effects of PFCs on human health. The following review describes both external and internal exposures to PFCs, the toxicokinetics (uptake, distribution, metabolism, excretion), and the toxicodynamics (acute toxicity, subacute and subchronic toxicities, chronic toxicity including carcinogenesis, genotoxicity and epigenetic effects, reproductive and developmental toxicities, neurotoxicity, effects on the endocrine system, immunotoxicity and potential modes of action, combinational effects, and epidemiological studies on perfluorinated compounds). (orig.)

  12. Subchronic toxicity study of corn silk with rats.

    Science.gov (United States)

    Wang, Cuina; Zhang, Tiehua; Liu, Jun; Lu, Shuang; Zhang, Cheng; Wang, Erlei; Wang, Zuozhao; Zhang, Yan; Liu, Jingbo

    2011-09-01

    Corn silk is a traditional herbal medicine in China, which has been used in many parts of the world for the treatment of edema as well as for cystitis, gout, kidney stones, nephritis, prostatitis and similar ailments. However, there is little scientific evidence about its safety. As a part of its safety assessment, a subchronic toxicity was performed in this paper. The subchronic toxicity was investigated in male and female Wistar rats by dietary administration at concentrations of 0.5%, 2.0% and 8.0% (w/w) for 90 days. Overall health, body weight, food consumption, hematology, blood chemistry, organ weights, gross and microscopic appearance of tissues were compared between test and control groups. A number of significant differences were seen between groups, but none of them was considered to be adverse. Based on the present study, the no-observed-adverse-effect level (NOAEL) of corn silk is at least 8.0% which corresponds to a mean daily corn silk intake of approximately 9.354 and 10.308 g/day/kg body weight for males and females, respectively. The results obtained in the present study suggest that consumption of corn silk has no adverse effects and support the safety of corn silk for humans. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  13. Summary introduction to environmental toxicology

    International Nuclear Information System (INIS)

    Heinzow, B.; Jessen, H.; Wendorff, D.

    1986-01-01

    The increasing environmental consciousness and the increasing public interest in environmental medicine and toxicology is much appreciated by the Research Institute for Environmental Toxicology. This information brochure gives the reader some insight into the importance of environmental toxicology and into the waste of the Research Institute. In response to the current situation, the authors have included an appendix on radiation protection. (orig./PW) [de

  14. High Throughput Transcriptomics @ USEPA (Toxicology ...

    Science.gov (United States)

    The ideal chemical testing approach will provide complete coverage of all relevant toxicological responses. It should be sensitive and specific It should identify the mechanism/mode-of-action (with dose-dependence). It should identify responses relevant to the species of interest. Responses should ideally be translated into tissue-, organ-, and organism-level effects. It must be economical and scalable. Using a High Throughput Transcriptomics platform within US EPA provides broader coverage of biological activity space and toxicological MOAs and helps fill the toxicological data gap. Slide presentation at the 2016 ToxForum on using High Throughput Transcriptomics at US EPA for broader coverage biological activity space and toxicological MOAs.

  15. Acute and sub-chronic toxicity evaluations of aqueous extract from stem bark of Grewia mollis (Malvaceae in rats

    Directory of Open Access Journals (Sweden)

    Pongri Adarki

    2017-09-01

    Full Text Available Introduction: Different parts of Grewia mollis Juss. (Malvaceae are commonly used in folk medicine to treat several ailments, including diarrhea, ulcers, rickets, cough and fever. Although several studies have proved its therapeutic effectiveness, there are very few toxicological studies on the plant. Objectives: This study was carried out to evaluate the acute and sub-chronic toxicity of the aqueous extract of G. mollis stem bark (GM in animals. Methods: In the acute study, rats were orally administrated with GM at doses of 150, 300, 600, 1200, 2400, 4800 and 9600 mg/kg to determine the oral medial lethal dose (LD50. In the chronic study, rats received three doses of GM (150, 300 and 600 mg/kg for 28 days. After the treatments, food intake, body weights, biochemical, hematological and histopathological parameters were analyzed. Results: The LD50 was estimated to be >9600 mg/kg. No significant alterations in the animal’s body weight gain, relative organs weight, serum biochemical analysis, hematological or histopathological analyses of liver, kidneys, lungs, heart and spleen were observed. Conclusions: The results of this study provided evidence that oral administration of GM at dose of 600 mg/kg is relatively safe in rats and may not exert severe toxic effects.

  16. Safety assessment of McB-E60 (extract of a Momordica sp.: Subchronic toxicity study in rats

    Directory of Open Access Journals (Sweden)

    Narendra S. Deshmukh

    Full Text Available Momordica charantia plant is consumed as a foodstuff in some south Asian curries while its extract preparations have been traditionally used for lowering blood glucose levels in patients with diabetes mellitus. Nutritional Health Institute Laboratories (NHIL, LLC, Florida informed that it patented a new plant McB, as an interhybrid of three plants of Momordica genus. The objective of the present study was to investigate potential adverse effects, if any, of McB-E60 (extract of a Momordica sp. in rats following subchronic administration. Sprague-Dawley rats (10/sex/group were administered via oral gavage 0 (control, 250, 500 and 1000 mg/kg body weight (bw/day of McB-E60 for 90 days. Additional 28-day recovery groups were maintained at control and high dose levels. No mortality or significant and adverse changes in clinical signs, neurological signs, body weight gain or feed intake were noted. No toxicologically significant changes in hematology, clinical chemistry, urinalysis and organ weights were noted. Gross and microscopic pathology examinations did not reveal treatment-related abnormalities. Any changes noted were incidental and within historical control ranges. Based on the results of this study, the No-Observed-Effect Level (NOEL for McB-E60 (extract of a Momordica sp. was determined as greater than 1000 mg/kg bw/day, the highest dose tested. Keywords: Dietary supplement, Safety, Toxicity

  17. The relative effectiveness of inhaled alpha- and beta-emitting radionuclides in producing lung cancer

    International Nuclear Information System (INIS)

    Boecker, B.B.; Hahn, F.F.; Muggenburg, B.A.; Guilmetter, R.A.; Griffith, W.C.; McClellan, R.O.

    1988-01-01

    Proper assessment of a long-term human health risks associated with inhaled radionuclides requires knowledge of dose to critical cells and tissues and relationships between dose and effect for different biological end points. Results from epidemiological studies of exposed human populations provided important information for such assessments. However, because the types of exposures are limited, these results need to be supplemented with more detailed information on dosimetry and biological effects available through studies in laboratory animals and in vitro systems. To provide health risk information for inhaled fission product and actinide aerosols, life-span studies are being conducted using beagle dogs and other species at the Lovelace Inhalation Toxicology Research Institute (ITRI). Results of two life-span studies in dogs involving inhalation of the beta emitter 91 Y in fused aluminosilicate particles or the alpha emitter 239 PuO 2 are reported here

  18. ACToR-AGGREGATED COMPUTATIONAL TOXICOLOGY ...

    Science.gov (United States)

    One goal of the field of computational toxicology is to predict chemical toxicity by combining computer models with biological and toxicological data. predict chemical toxicity by combining computer models with biological and toxicological data

  19. Sudden death caused by 1,1-difluoroethane inhalation.

    Science.gov (United States)

    Xiong, Zhenggang; Avella, Joseph; Wetli, Charles V

    2004-05-01

    A 20-year-old man was found dead on the floor next to a computer, with a nearly full can of "CRC Duster" dust remover located next to the deceased on the floor, and an empty can of the same product on the computer desk. Toxicologic evaluation using either gas chromatography/mass spectrometry (GC/MS) or gas chromatography/flame ionization detector (GC/FID) method identified the active ingredient 1,1-difluoroethane (Freon 152a) in all tissues analyzed. Tissue distribution studies revealed highest concentration in central blood, lung, and liver. It is believed that the 1,1-difluoroethane inhalation was the cause of death.

  20. Postmortem Biochemistry and Toxicology

    Directory of Open Access Journals (Sweden)

    Robert Flanagan

    2017-04-01

    Full Text Available The aim of postmortem biochemistry and toxicology is either to help establish the cause of death, or to gain information on events immediately before death. If self-poisoning is suspected, the diagnosis may be straightforward and all that could be required is confirmation of the agents involved. However, if the cause of death is not immediately obvious then suspicion of possible poisoning or of conditions such as alcoholic ketoacidosis is of course crucial. On the other hand, it may be important to investigate adherence to prescribed therapy, for example with anticonvulsants or antipsychotics, hence sensitive methods are required. Blood sampling (needle aspiration, peripheral vein, for example femoral, ideally after proximal ligation before opening the body minimizes the risk of sample contamination with, for example, gut contents or urine. Other specimens (stomach contents, urine, liver, vitreous humor may also be valuable and may be needed to corroborate unexpected or unusual findings in the absence of other evidence. The site of sampling should always be recorded. The availability of antemortem specimens should not necessarily preclude postmortem sampling. Appropriate sample preservation, transport, and storage are mandatory. Interpretation of analytical toxicology results must take into account what is known of the pharmacokinetics and toxicology of the agent(s in question, the circumstances under which death occurred including the mechanism of exposure, and other factors such as the stability of the analyte(s and the analytical methods used. It is important to realise that changes may occur in the composition of body fluids, even peripheral blood, after death. Such changes are likely to be greater after attempted resuscitation, and with centrally-acting drugs with large volumes of distribution given chronically, and may perhaps be minimised by prompt refrigeration of the body and performing the autopsy quickly.

  1. Toxicology of freshwater cyanobacteria.

    Science.gov (United States)

    Liyanage, H M; Arachchi, D N Magana; Abeysekara, T; Guneratne, L

    2016-07-02

    Many chemical contaminants in drinking water have been shown to cause adverse health effects in humans after prolonged exposure. Cyanobacteria are one of the most potent and diverse groups of photosynthetic prokaryotes. One key component of cyanobacterial success in the environment is the production of potent toxins as secondary metabolites, which have been responsible for numerous adverse health impacts in humans. Anthropogenic activities have led to the increase of eutrophication in freshwater bodies' worldwide, causing cyanobacterial blooms to become more frequent. The present article will discuss about harmful cyanobacteria and their toxicology with special references to microcystin, nodularin, and cylindrospermopsin.

  2. Pharmacogenetics and forensic toxicology.

    Science.gov (United States)

    Musshoff, Frank; Stamer, Ulrike M; Madea, Burkhard

    2010-12-15

    Large inter-individual variability in drug response and toxicity, as well as in drug concentrations after application of the same dosage, can be of genetic, physiological, pathophysiological, or environmental origin. Absorption, distribution and metabolism of a drug and interactions with its target often are determined by genetic differences. Pharmacokinetic and pharmacodynamic variations can appear at the level of drug metabolizing enzymes (e.g., the cytochrome P450 system), drug transporters, drug targets or other biomarker genes. Pharmacogenetics or toxicogenetics can therefore be relevant in forensic toxicology. This review presents relevant aspects together with some examples from daily routines. Copyright © 2010. Published by Elsevier Ireland Ltd.

  3. E-submission Format for Sub-chronic and Chronic Studies

    Science.gov (United States)

    The purpose of this document is to suggest the format for final reports and to provide instructions for creation of Adobe PDF electronic submission documents for electronic submission of sub-chronic and chronic studies for pesticides.

  4. Acute and subchronic oral toxicity studies in rats with nanoscale and pigment grade titanium dioxide particles.

    Science.gov (United States)

    Warheit, D B; Brown, S C; Donner, E M

    2015-10-01

    adverse toxicological effects. Apart from reporting the findings of these three studies, this publication also focuses on additional critical issues associated with particle and nanotoxicology studies. First, describing the detailed methodology requirements and rigor upon which the standardized OECD 408 guideline subchronic oral toxicity studies are conducted. Moreover, an attempt is made to reconcile the complex issue of particle size distribution as it relates to measurements of nanoscale and pigment-grade TiO2 particles. Clearly this has been a confusing issue and often misrepresented in the media and the scientific literature. It is clear that the particle-size distribution for pigment-grade TiO2, contains a small ("tail") component of nanoscale particles (i.e., 21% by particle number and TiO2 Test Material sample in the 90-day study. Finally, it seems reasonable to conclude that the study findings should be considered for read-across purposes to food-grade TiO2 particles (e.g., E171), as the physicochemical characteristics are quite similar. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Food hypersensitivity by inhalation

    Directory of Open Access Journals (Sweden)

    Bahna Sami L

    2009-02-01

    Full Text Available Abstract Though not widely recognized, food hypersensitivity by inhalation can cause major morbidity in affected individuals. The exposure is usually more obvious and often substantial in occupational environments but frequently occurs in non-occupational settings, such as homes, schools, restaurants, grocery stores, and commercial flights. The exposure can be trivial, as in mere smelling or being in the vicinity of the food. The clinical manifestations can vary from a benign respiratory or cutaneous reaction to a systemic one that can be life-threatening. In addition to strict avoidance, such highly-sensitive subjects should carry self-injectable epinephrine and wear MedicAlert® identification. Asthma is a strong predisposing factor and should be well-controlled. It is of great significance that food inhalation can cause de novo sensitization.

  6. Inhalation of uranium ores

    International Nuclear Information System (INIS)

    Stuart, B.O.; Jackson, P.O.

    1975-01-01

    In previous studies the biological dispositions of individual long-lived alpha members of the uranium chain ( 238 U, 234 U and 230 Th) were determined during and following repeated inhalation exposures of rats to pitchblende (26 percent U 3 O 8 ) ore. Although finely dispersed ore in secular equilibrium was inhaled, 230 Th/ 234 U radioactivity ratios in the lungs rose from 1.0 to 2.5 during 8 weeks of exposures and increased to 9.2 by four months after cessation of exposures. Marked non-equilibrium levels were also found in the tracheobronchial lymph nodes, kidneys, liver, and femur. Daily exposures of beagle dogs to high levels of this ore for 8 days resulted in lung 230 Th/ 234 U ratios of >2.0. Daily exposures of dogs to lower levels (0.1 mg/1) for 6 months, with sacrifice 15 months later, resulted in lung and thoracic lymph node 230 Th/ 234 U ratios ranging from 3.6 to 9 and nearly 7, respectively. The lungs of hamsters exposed to carnotite (4 percent U 3 O 8 ) ore in current lifespan studies show 230 Th/ 234 U ratios as high as 2.0 during daily inhalation of this ore in secular equilibrium. Beagle dogs sacrificed after several years of daily inhalations of the same carnotite ore plus radon daughters also showed marked non-equilibrium ratios of 230 Th/ 234 U, ranging from 5.6 to 7.4 in lungs and 6.2 to 9.1 in thoracic lymph nodes. This pattern of higher retention of 230 Th than 234 U in lungs, thoracic lymph nodes, and other tissues is thus consistent for two types of uranium ore among several species and suggests a reevaluation of maximum permissible air concentrations of ore, currently based only on uranium content

  7. Inhaled transuranics in rodents

    International Nuclear Information System (INIS)

    Sanders, C.L.

    1983-01-01

    This project examines the interactions of external and internal radiation from mixtures of radionuclides present within the nuclear fuel inventory. The objective of the project is to evaluate the effects of mixed radiation insults, using key radiation sources as indicative of overall processes that may occur following release of nuclear fuel into the air. Previously initiated studies of immunological effects of plutonium inhalation are also being completed as part of this project

  8. Toxicological evaluation of a novel umami flavour compound: 2-(((3-(2,3-Dimethoxyphenyl-1H-1,2,4-triazol-5-ylthiomethylpyridine

    Directory of Open Access Journals (Sweden)

    Donald S. Karanewsky

    Full Text Available A toxicological evaluation of a umami flavour compound, 2-(((3-(2,3-dimethoxyphenyl-1H-1,2,4-triazol-5-ylthiomethylpyridine (S3643; CAS 902136-79-2, was completed for the purpose of assessing its safety for use in food and beverage applications. S3643 undergoes extensive oxidative metabolism in vitro with rat microsomes producing the S3643-sulfoxide and 4′-hydroxy-S3643 as the major metabolites. In incubations with human microsomes, the O-demethyl-S3643 and S3643-sulfoxide were produced as the major metabolites. In pharmacokinetic studies in rats, the S3643-sulfoxide represents the dominant biotransformation product. S3643 was not found to be mutagenic or clastogenic in vitro, and did not induce micronuclei in CHO-WBL cells. In subchronic oral toxicity studies in rats, the no-observed-adverse-effect-level (NOAEL for S3643 was 100 mg/kg bw/day (highest dose tested when administered in the diet for 90 consecutive days. Keywords: Umami flavour, S3643, FEMA GRAS, Subchronic toxicological evaluation, Genetic toxicological evaluation

  9. Reproduction and subchronic feeding study of carnauba wax in rats.

    Science.gov (United States)

    Parent, R A; Re, T A; Babish, J G; Cox, G E; Voss, K A; Becci, P J

    1983-02-01

    The reproductive performance of Wistar rats fed carnauba wax at levels of 0.1, 0.3 or 1% in the diet and the effects of subchronic administration of carnauba wax at these dose levels on the resultant progeny were studied. Reproductive indices, body-weight gain, food consumption, haematological and clinical chemical data, ophthalmic, gross and histopathological examinations were used to study the possible toxic or pathological effects. Serum free fatty acid levels were found to be decreased in male and female rats fed carnauba wax at dietary levels of 0.3 and 1.0%. No other effects of feeding carnauba wax at levels up to 1.0% of the diet were observed.

  10. A plastic stabilizer dibutyltin dilaurate induces subchronic neurotoxicity in rats☆

    Science.gov (United States)

    Jin, Minghua; Song, Peilin; Li, Na; Li, Xuejun; Chen, Jiajun

    2012-01-01

    Dibutyltin dilaurate functions as a stabilizer for polyvinyl chloride. In this study, experimental rats were intragastrically administered 5, 10, or 20 mg/kg dibutyltin dilaurate to model sub-chronic poisoning. After exposure, our results showed the activities of superoxide dismutase and glutathione peroxidase decreased in rat brain tissue, while the malondialdehyde and nitric oxide content, as well as nitric oxide synthase activity in rat brain tissue increased. The cell cycle in the right parietal cortex was disordered and the rate of apoptosis increased. DNA damage was aggravated in the cerebral cortex, and the ultrastructure of the right parietal cortex tissues was altered. The above changes became more apparent with exposure to increasing doses of dibutyltin dilaurate. Our experimental findings confirmed the neurotoxicity of dibutyltin dilaurate in rat brain tissues, and demonstrated that the poisoning was dose-dependent. PMID:25538742

  11. Pulmonary retention and tissue distribution of 239Pu nitrate in F344 rats and syrian hamsters inhaling carbon tetrachloride

    International Nuclear Information System (INIS)

    Benson, J.M.; Barr, E.B.; Lundgren, D.L.; Nikula, K.J.

    1994-01-01

    Carbon tetrachloride (CCl 4 ) has been used extensively in the nuclear weapons industry, so it is possible that nuclear plant workers have been exposed to CCl 4 and plutonium compounds. Potential for future exposure exists during open-quotes cleanupclose quotes operations at weapon production sites such as the Hanford, Washington, and Rocky Flats, Colorado, facilities. The current Threshold Limit Value for CCl 4 is 5 ppm; however, concentrations of CCl 4 occurring in the nuclear weapons facilities over the past 40-50 y are unknown and may have exceeded this value. The pilot study described in this report is designed to determine whether subchronic inhalation of CCl 4 by CDF register (F-344)/CrlBR rats and Syrian golden hamsters, at concentrations expected to produce some histologic changes in liver, alters the hepatic retention and toxic effects of inhaled 239 Pu nitrate 239 Pu(NO 3 ) 4

  12. Airway irritation, inflammation, and toxicity in mice following inhalation of metal oxide nanoparticles

    DEFF Research Database (Denmark)

    Larsen, Søren T; Jackson, Petra; Poulsen, Steen S

    2016-01-01

    Metal oxide nanoparticles are used in a broad range of industrial processes and workers may be exposed to aerosols of the particles both during production and handling. Despite the widespread use of these particles, relatively few studies have been performed to investigate the toxicological effects...... in the airways following inhalation. In the present study, the acute (24 h) and persistent (13 weeks) effects in the airways after a single exposure to metal oxide nanoparticles were studied using a murine inhalation model. Mice were exposed 60 min to aerosols of either ZnO, TiO2, Al2O3 or CeO2 and the deposited...

  13. Perlite toxicology and epidemiology – a review

    Science.gov (United States)

    Niebo, Ron; McConnell, Ernest E.

    2014-01-01

    Perlite is a generic name for an amorphous volcanic alumina–silicate rock that expands by a factor of 4–20 when rapidly heated to 1400–1800 °F (760–980 °C). Both the ore and the expanded product have extensive and widespread commercial applications. Limited data on the toxicology of perlite in animal studies indicate that the LD50 (oral ingestion) is more than 10 g/kg and, from a chronic inhalation study in guinea pigs and rats, that the NOAEL for the inhalation pathway is 226 mg/m3. Health surveillance studies of workers in US perlite mines and expansion plants (including some workers exposed to levels greater than prevailing occupational exposure limits (OELs) conducted over 20 years indicate that the respiratory health of workers is not adversely affected. Studies in Turkish mines and expanding plants had generally similar results, but are more difficult to interpret because of high smoking rates in these populations. A recent mortality study of permanent residents of the island of Milos (Greece) exposed to various mining dusts (including perlite) resulted in non-significant increases in standard mortality ratios for pneumonia and chronic obstructive pulmonary disease (COPD), whereas a companion morbidity study revealed elevated odds ratios for allergic rhinitis, pneumonia, and COPD when compared to another industrial area of Greece. Residents were exposed to other mining dusts and other possible causes or contributing factors and no ambient monitoring data were presented so it is not possible to use this study for risk calculations of perlite-exposed populations. Perlite is regulated as a “nuisance dust” in most countries. PMID:24601903

  14. Nuclear toxicology at CEA

    International Nuclear Information System (INIS)

    Giustranti, C.

    2001-01-01

    CEA (French commission of atomic energy) has launched a new program dedicated to the study of the transfer of heavy metals and some radionuclides from environment to living beings. The substances that will be studied, are those that are involved in research, medical activities, and in nuclear industry. It means iodine, technetium, trans-uranides (uranium and plutonium), fission products (iodine, cesium), carbon, cobalt, boron and beryllium. This program is composed of 2 axis: the first one concerns the bio-geo-chemical cycles that are involved in transfer and the second axis deals with the detoxication processes that appear in animal and man cells. This program will rely on the strong competencies of CEA in chemistry, radiochemistry, biology, physiology and toxicology. (A.C.)

  15. Emerging approaches in predictive toxicology.

    Science.gov (United States)

    Zhang, Luoping; McHale, Cliona M; Greene, Nigel; Snyder, Ronald D; Rich, Ivan N; Aardema, Marilyn J; Roy, Shambhu; Pfuhler, Stefan; Venkatactahalam, Sundaresan

    2014-12-01

    Predictive toxicology plays an important role in the assessment of toxicity of chemicals and the drug development process. While there are several well-established in vitro and in vivo assays that are suitable for predictive toxicology, recent advances in high-throughput analytical technologies and model systems are expected to have a major impact on the field of predictive toxicology. This commentary provides an overview of the state of the current science and a brief discussion on future perspectives for the field of predictive toxicology for human toxicity. Computational models for predictive toxicology, needs for further refinement and obstacles to expand computational models to include additional classes of chemical compounds are highlighted. Functional and comparative genomics approaches in predictive toxicology are discussed with an emphasis on successful utilization of recently developed model systems for high-throughput analysis. The advantages of three-dimensional model systems and stem cells and their use in predictive toxicology testing are also described. © 2014 Wiley Periodicals, Inc.

  16. Mass Spectrometry Applications for Toxicology.

    Science.gov (United States)

    Mbughuni, Michael M; Jannetto, Paul J; Langman, Loralie J

    2016-12-01

    Toxicology is a multidisciplinary study of poisons, aimed to correlate the quantitative and qualitative relationships between poisons and their physiological and behavioural effects in living systems. Other key aspects of toxicology focus on elucidation of the mechanisms of action of poisons and development of remedies and treatment plans for associated toxic effects. In these endeavours, Mass spectrometry (MS) has become a powerful analytical technique with a wide range of application used in the Toxicological analysis of drugs, poisons, and metabolites of both. To date, MS applications have permeated all fields of toxicology which include; environmental, clinical, and forensic toxicology. While many different analytical applications are used in these fields, MS and its hyphenated applications such as; gas chromatography MS (GC-MS), liquid chromatography MS (LC-MS), inductively coupled plasma ionization MS (ICP-MS), tandem mass spectrometry (MS/MS and MS n ) have emerged as powerful tools used in toxicology laboratories. This review will focus on these hyphenated MS technologies and their applications for toxicology.

  17. Mass Spectrometry Applications for Toxicology

    Science.gov (United States)

    Mbughuni, Michael M.; Jannetto, Paul J.

    2016-01-01

    Toxicology is a multidisciplinary study of poisons, aimed to correlate the quantitative and qualitative relationships between poisons and their physiological and behavioural effects in living systems. Other key aspects of toxicology focus on elucidation of the mechanisms of action of poisons and development of remedies and treatment plans for associated toxic effects. In these endeavours, Mass spectrometry (MS) has become a powerful analytical technique with a wide range of application used in the Toxicological analysis of drugs, poisons, and metabolites of both. To date, MS applications have permeated all fields of toxicology which include; environmental, clinical, and forensic toxicology. While many different analytical applications are used in these fields, MS and its hyphenated applications such as; gas chromatography MS (GC-MS), liquid chromatography MS (LC-MS), inductively coupled plasma ionization MS (ICP-MS), tandem mass spectrometry (MS/MS and MSn) have emerged as powerful tools used in toxicology laboratories. This review will focus on these hyphenated MS technologies and their applications for toxicology. PMID:28149262

  18. COMPUTATIONAL TOXICOLOGY-WHERE IS THE DATA? ...

    Science.gov (United States)

    This talk will briefly describe the state of the data world for computational toxicology and one approach to improve the situation, called ACToR (Aggregated Computational Toxicology Resource). This talk will briefly describe the state of the data world for computational toxicology and one approach to improve the situation, called ACToR (Aggregated Computational Toxicology Resource).

  19. Ninth Triennial Toxicology Salary Survey.

    Science.gov (United States)

    Gad, Shayne Cox; Sullivan, Dexter Wayne

    2016-01-01

    This survey serves as the ninth in a series of toxicology salary surveys conducted at 3-year intervals and beginning in 1988. An electronic survey instrument was distributed to 5919 individuals including members of the Society of Toxicology, American College of Toxicology, and 23 additional professional organizations. Question items inquired about gender, age, degree, years of experience, certifications held, areas of specialization, society membership, employment and income. Overall, 1293 responses were received (response rate 21.8%). The results of the 2014 survey provide insight into the job market and career path for current and future toxicologists. © The Author(s) 2016.

  20. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... Controlling Tools for Control Triggers Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers ... inhaler with a spacer Your browser does not support iframes Using a metered dose inhaler with a ...

  1. American College of Medical Toxicology

    Science.gov (United States)

    ... Publications Journal of Medical Toxicology About ACMT About Us History of ACMT ACMT Fact Sheet Strategic Plan ACMT ... Policies IJMT JMT Editorial Board About ACMT About Us History of ACMT ACMT Fact Sheet Strategic Plan ACMT ...

  2. Aggregated Computational Toxicology Resource (ACTOR)

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Aggregated Computational Toxicology Resource (ACTOR) is a database on environmental chemicals that is searchable by chemical name and other identifiers, and by...

  3. Predictive toxicology in drug safety

    National Research Council Canada - National Science Library

    Xu, Jinghai J; Urban, Laszlo

    2011-01-01

    .... It provides information on the present knowledge of drug side effects and their mitigation strategy during drug discovery, gives guidance for risk assessment, and promotes evidence-based toxicology...

  4. Aggregated Computational Toxicology Online Resource

    Data.gov (United States)

    U.S. Environmental Protection Agency — Aggregated Computational Toxicology Online Resource (AcTOR) is EPA's online aggregator of all the public sources of chemical toxicity data. ACToR aggregates data...

  5. Toxicology of Biodiesel Combustion products

    Science.gov (United States)

    1. Introduction The toxicology of combusted biodiesel is an emerging field. Much of the current knowledge about biological responses and health effects stems from studies of exposures to other fuel sources (typically petroleum diesel, gasoline, and wood) incompletely combusted. ...

  6. Mass Spectrometry Applications for Toxicology

    OpenAIRE

    Mbughuni, Michael M.; Jannetto, Paul J.; Langman, Loralie J.

    2016-01-01

    Toxicology is a multidisciplinary study of poisons, aimed to correlate the quantitative and qualitative relationships between poisons and their physiological and behavioural effects in living systems. Other key aspects of toxicology focus on elucidation of the mechanisms of action of poisons and development of remedies and treatment plans for associated toxic effects. In these endeavours, Mass spectrometry (MS) has become a powerful analytical technique with a wide range of application used i...

  7. Behavioral assays in environmental toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, B.

    1979-01-01

    Environmental toxicology is too permeated by questions about how the whole organism functions to abandon intact animals as test systems. Behavior does not participate as a single entity or discipline. It ranges across the total spectrum of functional toxicity, from tenuous subjective complaints to subtle sensory and motor disturbances demanding advanced instrumentation for their evaluation. Three facets of behavioral toxicology that illustrate its breadth of interests and potential contributions are discussed.

  8. A practice analysis of toxicology.

    Science.gov (United States)

    Wood, Carol S; Weis, Christopher P; Caro, Carla M; Roe, Amy

    2016-12-01

    In 2015, the American Board of Toxicology (ABT), with collaboration from the Society of Toxicology (SOT), in consultation with Professional Examination Service, performed a practice analysis study of the knowledge required for general toxicology. The purpose of this study is to help assure that the examination and requirements for attainment of Diplomate status are relevant to modern toxicology and based upon an empirical foundation of knowledge. A profile of the domains and tasks used in toxicology practice was developed by subject-matter experts representing a broad range of experiences and perspectives. An on-line survey of toxicologists, including Diplomates of the ABT and SOT members, confirmed the delineation. Results of the study can be used to improve understanding of toxicology practice, to better serve all toxicologists, and to present the role of toxicologists to those outside the profession. Survey results may also be used by the ABT Board of Directors to develop test specifications for the certifying examination and will be useful for evaluating and updating the content of professional preparation, development, and continuing education programs. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Reporting a sudden death due to accidental gasoline inhalation.

    Science.gov (United States)

    Martínez, María Antonia; Ballesteros, Salomé; Alcaraz, Rafael

    2012-02-10

    The investigation of uncertain fatalities requires accurate determination of the cause of death, with assessment of all factors that may have contributed to it. Gasoline is a complex and highly variable mixture of aliphatic and aromatic hydrocarbons that can lead to cardiac arrhythmias due to sensitization of the myocardium to catecholamines or acts as a simple asphyxiant if the vapors displace sufficient oxygen from the breathing atmosphere. This work describes a sudden occupational fatality involving gasoline. The importance of this petroleum distillate detection and its quantitative toxicological significance is discussed using a validated analytical method. A 51 year-old Caucasian healthy man without significant medical history was supervising the repairs of the telephone lines in a manhole near to a gas station. He died suddenly after inhaling gasoline vapors from an accidental leak. Extensive blistering and peeling of skin were observed on the skin of the face, neck, anterior chest, upper and lower extremities, and back. The internal examination showed a strong odor of gasoline, specially detected in the respiratory tract. The toxicological screening and quantitation of gasoline was performed by means of gas chromatography with flame ionization detector and confirmation was performed using gas chromatography-mass spectrometry. Disposition of gasoline in different tissues was as follows: heart blood, 35.7 mg/L; urine, not detected; vitreous humor, 1.9 mg/L; liver, 194.7 mg/kg; lung, 147.6 mg/kg; and gastric content, 116,6 mg/L (2.7 mg total). Based upon the toxicological data along with the autopsy findings, the cause of death was determined to be gasoline poisoning and the manner of death was accidental. We would like to alert on the importance of testing for gasoline, and in general for volatile hydrocarbons, in work-related sudden deaths involving inhalation of hydrocarbon vapors and/or exhaust fumes. Copyright © 2011 Elsevier Ireland Ltd. All rights

  10. Ethanol Forensic Toxicology.

    Science.gov (United States)

    Perry, Paul J; Doroudgar, Shadi; Van Dyke, Priscilla

    2017-12-01

    Ethanol abuse can lead to negative consequences that oftentimes result in criminal charges and civil lawsuits. When an individual is suspected of driving under the influence, law enforcement agents can determine the extent of intoxication by measuring the blood alcohol concentration (BAC) and performing a standardized field sobriety test. The BAC is dependent on rates of absorption, distribution, and elimination, which are influenced mostly by the dose of ethanol ingested and rate of consumption. Other factors contributing to BAC are gender, body mass and composition, food effects, type of alcohol, and chronic alcohol exposure. Because of individual variability in ethanol pharmacology and toxicology, careful extrapolation and interpretation of the BAC is needed, to justify an arrest and assignment of criminal liability. This review provides a summary of the pharmacokinetic properties of ethanol and the clinical effects of acute intoxication as they relate to common forensic questions. Concerns regarding the extrapolation of BAC and the implications of impaired memory caused by alcohol-induced blackouts are discussed. © 2017 American Academy of Psychiatry and the Law.

  11. [Toxicologic blood emergency screening].

    Science.gov (United States)

    Cohen, Sabine; Manat, Aurélie; Dumont, Benoit; Bévalot, Fabien; Manchon, Monique; Berny, Claudette

    2010-01-01

    In order to overcome the stop marketing by Biorad company of automated high performance liquid chromatograph with UV detection (Remedi), we developed a gas chromatography-mass spectrometry (GC-MS) to detect and to give an approximation of the overdose of molecules frequently encountered in drug intoxications. Therefore two hundred eighty seventeen blood samples were collected over a period of one year and allowed us to evaluate and compare the performance of these two techniques. As identification, GC-MS does not identify all molecules detected by Remedi in 24.2% of cases; there is a lack of sensitivity for opiates and the systematic absence of certain molecules such as betablockers. However, in 75.8% of cases the GC-MS detects all molecules found by Remedi and other molecules such as meprobamate, paracetamol, benzodiazepines and phenobarbital. The concentrations obtained are interpreted in terms of overdose showed 15.7% of discrepancy and 84.3% of concordance between the two techniques. The GC-MS technique described here is robust, fast and relatively simple to implement; the identification is facilitated by macro commands and the semi quantification remains manual. Despite a sequence of cleaning the column after each sample, carryover of a sample to the next remains possible. This technique can be used for toxicologic screening in acute intoxications. Nevertheless it must be supplemented by a HPLC with UV detection if molecules such as betablockers are suspected.

  12. Toxicology of plutonium

    International Nuclear Information System (INIS)

    Bair, W.J.

    1974-01-01

    Data are reviewed from studies on the toxicity of Pu in experimental animals. Of the several plutonium isotopes, only 238 Pu and 239 Pu have been studied well. Sufficient results have been obtained to show that the behavior of 238 Pu in biological systems and the resulting biological effects cannot be precisely predicted from studies of 239 Pu. This probably applies also to other radiologically important plutonium isotopes which have half-lives ranging from 45 days to 10 7 years and decay by β-emission, electron capture, and spontaneous fission, as well as by emission of α-particles. All the biological effects of plutonium described in this review are attributed to alpha-particle radiation emitted by the plutonium. However, since plutonium is a chemically active heavy metal, one cannot ignore the possibility of chemical toxicity of the low-specific-activity isotopes, 239 Pu, 242 Pu, and 244 Pu. The preponderance of our knowledge of plutonium toxicology has come from short-term studies of relatively high dosage levels in several animal species. The consequences of high-level internal exposures can be predicted with confidence in experimental animals and probably also in man. However, considering the care with which plutonium is handled in the nuclear industry, a high-level contamination event is unlikely. Considerably less is known about the long-term effects of low levels of contamination. (250 references) (U.S.)

  13. Exubera. Inhale therapeutic systems.

    Science.gov (United States)

    Bindra, Sanjit; Cefalu, William T

    2002-05-01

    Inhale, in colaboration with Pfizer and Aventis Pharma (formerly Hoechst Marion Roussel; HMR), is developing an insulin formulation utilizing its pulmonary delivery technology for macromolecules for the potential treatment of type I and II diabetes. By July 2001, the phase III program had been completed and the companies had begun to assemble data for MAA and NDA filings; however, it was already clear at this time that additional data might be required for filing. By December 2001, it had been decided that the NDA should include an increased level of controlled, long-term pulmonary safety data in diabetic patients and a major study was planned to be completed in 2002, with the NDA filed thereafter (during 2002). US-05997848 was issued to Inhale Therapeutic Systems in December 1999, and corresponds to WO-09524183, filed in February 1995. Equivalent applications have appeared to date in Australia, Brazil, Canada, China, Czech Republic, Europe, Finland, Hungary, Japan, Norway, New Zealand, Poland and South Africa. This family of applications is specific to pulmonary delivery of insulin. In February 1999, Lehman Brothers gave this inhaled insulin a 60% probability of reaching market, with a possible launch date of 2001. The analysts estimated peak sales at $3 billion in 2011. In May 2000, Aventis predicted that estimated peak sales would be in excess of $1 billion. In February 2000, Merrill Lynch expected product launch in 2002 and predicted that it would be a multibillion-dollar product. Analysts Merril Lynch predicted, in September and November 2000, that the product would be launched by 2002, with sales in that year of e75 million, rising to euro 500 million in 2004. In April 2001, Merrill Lynch predicted that filing for this drug would occur in 2001. Following the report of the potential delay in regulatory filing, issued in July 2001, Deutsche Banc Alex Brown predicted a filing would take place in the fourth quarter of 2002 and launch would take place in the first

  14. Toxicology Studies on Lewisite and Sulfur Mustard Agents: Subchronic Toxicity of Sulfur Mustard (HD) In Rats Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Sasser, L. B.; Miller, R. A.; Kalkwarf, D, R.; Buschbom, R. L.; Cushing, J. A.

    1989-06-30

    Occupational health standards have not been established for sulfur mustard [bis(2- chlorethyl)-sulfide], a strong alkylating agent with known mutagenic properties. Seventytwo Sprague-Dawley rats of each sex, 6-7 weeks old, were divided into six groups (12/group/ sex) and gavaged with either 0, 0.003 , 0.01 , 0.03 , 0.1 or 0.3 mg/kg of sulfur mustard in sesame oil 5 days/week for 13 weeks. No dose-related mortality was observed. A significant decrease (P ( 0.05) in body weight was observed in both sexes of rats only in the 0.3 mg/kg group. Hematological evaluations and clinical chemistry measurements found no consistent treatment-related effects at the doses studied. The only treatment-related lesion associated with gavage exposure upon histopathologic evaluation was epithelial hyperplasia of the forestomach of both sexes at 0.3 mg/kg and males at 0.1 mg/kg. The hyperplastic change was minimal and characterized by cellular disorganization of the basilar layer, an apparent increase in mitotic activity of the basilar epithelial cells, and thickening of the epithelial layer due to the apparent increase in cellularity. The estimated NOEL for HD in this 90-day study is 0.1 mg/kg/day when administered orally.

  15. Sub-chronic toxicological evaluation of cleistanthin A and cleistanthin B from the leaves of Cleistanthus collinus (Roxb.

    Directory of Open Access Journals (Sweden)

    Subramani Parasuraman

    2014-01-01

    Conclusion: The present study concludes that both cleistanthin A and cleistanthin B exert severe toxic effects on lungs, brain, liver, heart and kidneys. They do not cause any significant pathological change in the reproductive system; neither do they induce neurodegenerative changes in brain. When compared to cleistanthin A, cleistanthin B is more toxic in rats.

  16. Toxicological responses of red-backed salamanders (Plethodon cinereus) to subchronic soil exposures of 2,4-dinitrotoluene

    International Nuclear Information System (INIS)

    Johnson, Mark S.; Suski, Jamie; Bazar, Matthew A.

    2007-01-01

    Dinitrotoluenes are used as propellants and in explosives by the military and as such have been found at relatively high concentrations in the soil. To determine whether concentrations of 2,4-dinitrotoluene (2,4-DNT) in soil are toxic to amphibians, 100 red-backed salamanders (Plethodon cinereus) were exposed to either 1500, 800, 200, 75 or 0 mg 2,4-DNT/kg soil for 28 days and evaluated for indicators of toxicity. Concentrations of 2,4-DNT were less than targets and varied with time. Most salamanders exposed to concentrations exceeding 1050 mg/kg died or were moribund within the first week. Salamanders exposed to soil concentrations exceeding 345 mg/kg lost >6% of their body mass though no mortality occurred. Overt effects included a reduction in feed consumption and an increase in bucco-pharyngeal oscillations in salamanders. These results suggest that only high soil concentrations of 2,4-DNT have the potential to cause overtly toxic effects in terrestrial salamanders. - Exposures of 2,4-dinitrotoluene in soil exceeding 345 mg/kg causes toxicity to P. cinereus

  17. Subchronic toxicity of Baltic herring oil and its fractions in the rat II: Clinical observations and toxicological parameters

    NARCIS (Netherlands)

    Stern, N.H.; Oberg, M.; Casabona, H.; Trossvik, C.; Manzoor, E.; Johansson, N.; Lind, M.; Orberg, J.; Feinstein, R.; Johansson, A.; Chu, I.; Poon, R.; Yagminas, A.; Brouwer, A.; Jones, B.; Hakansson, H.

    2002-01-01

    This study aimed to increase the knowledge about the toxicity of fish-derived organohalogen pollutants in mammals. The strategy chosen was to separate organohalogen pollutants derived from Baltic herring (Clupea harengus) fillet, in order to obtain fractions with differing proportions of identified

  18. Proteomic analysis of rat cerebral cortex following subchronic acrolein toxicity.

    Science.gov (United States)

    Rashedinia, Marzieh; Lari, Parisa; Abnous, Khalil; Hosseinzadeh, Hossein

    2013-10-01

    Acrolein, a member of reactive α,β-unsaturated aldehydes, is a major environmental pollutant. Acrolein is also produced endogenously as a toxic by-product of lipid peroxidation. Because of high reactivity, acrolein may mediate oxidative damages to cells and tissues. It has been shown to be involved in a wide variety of pathological states including pulmonary, atherosclerosis and neurodegenerative diseases. In this study we employed proteomics approach to investigate the effects of subchronic oral exposures to 3mg/kg of acrolein on protein expression profile in the brain of rats. Moreover effects of acrolein on malondialdehyde (MDA) levels and reduced glutathione (GSH) content were investigated. Our results revealed that treatment with acrolein changed levels of several proteins in diverse physiological process including energy metabolism, cell communication and transport, response to stimulus and metabolic process. Interestingly, several differentially over-expressed proteins, including β-synuclein, enolase and calcineurin, are known to be associated with human neurodegenerative diseases. Changes in the levels of some proteins were confirmed by Western blot. Moreover, acrolein increases the level of MDA, as a lipid peroxidation biomarker and decreased GSH concentrations, as a non-enzyme antioxidant in the brain of acrolein treated rats. These findings suggested that acrolein induces the oxidative stress and lipid peroxidation in the brain, and so that may contribute to the pathophysiology of neurological disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Extracorporeal Membrane Oxygenation (ECMO) for Severe Toxicological Exposures: Review of the Toxicology Investigators Consortium (ToxIC).

    Science.gov (United States)

    Wang, G S; Levitan, R; Wiegand, T J; Lowry, J; Schult, R F; Yin, S

    2016-03-01

    Although there have been many developments related to specific strategies for treating patients after poisoning exposures, the mainstay of therapy remains symptomatic and supportive care. One of the most aggressive supportive modalities is extracorporeal membrane oxygenation (ECMO). Our goal was to describe the use of ECMO for toxicological exposures reported to the American College of Medical Toxicology (ACMT) Toxicology Investigators Consortium (ToxIC). We performed a retrospective review of the ACMT ToxIC Registry from January 1, 2010 to December 31, 2013. Inclusion criteria included patients aged 0 to 89 years, evaluated between January 2010 through December 2013, and received ECMO for toxicological exposure. There were 26,271 exposures (60 % female) reported to the ToxIC Registry, 10 (0.0004 %) received ECMO: 4 pediatric (18 years). Time of initiation of ECMO ranged from 4 h to 4 days, with duration from 15 h to 12 days. Exposures included carbon monoxide/smoke inhalation (2), bitter almonds, methanol, and several medications including antihistamines (2), antipsychotic/antidepressant (2), cardiovascular drugs (2), analgesics (2), sedative/hypnotics (2), and antidiabetics (2). Four ECMO patients received cardiopulmonary resuscitation (CPR) during their hospital course, and the overall survival rate was 80 %. ECMO was rarely used for poisoning exposures in the ACMT ToxIC Registry. ECMO was utilized for a variety of ages and for pharmaceutical and non-pharmaceutical exposures. In most cases, ECMO was administered prior to cardiovascular failure, and survival rate was high. If available, ECMO may be a valid treatment modality.

  20. Subchronic toxicity of Nile tilapia with different exposure routes to Microcystis aeruginosa: Histopathology, liver functions, and oxidative stress biomarkers

    Directory of Open Access Journals (Sweden)

    H. M. R. Abdel-Latif

    2017-08-01

    Full Text Available Background: Toxic cyanobacterial blooms (Microcystis aeruginosa contains microcystins [MCs] have been reported to induce clinicopathological alterations as well as different oxidative stress in aquatic biota. Aim: Three-week subchronic exposure experiment was carried out on Nile tilapia, to determine their effects on fish behavior, tissues, liver functions, antioxidant enzymes, and lipid peroxidation. Materials and Methods: Fish were exposed to four main treatments; orally fed diet plus toxic cells of M. aeruginosa (containing 3500 μg/g MC-LR, immersion in 500 μg MC-LR/L, intraperitoneal injection of M. aeruginosa MC-LR with a dose of 0.1 ml of extracted toxin at a dose of 200 μg/kg bwt, and the fourth one served as a control group, then the fish were sacrificed at the end of 3rd week of exposure. Results: The results revealed no recorded mortality with obvious behavioral changes and an enlarged liver with the congested gall bladder. Histopathology demonstrated fragmentation, hyalinization, and necrosis of the subcutaneous musculature marked fatty degeneration, and vacuolation of hepatopancreatic cells with adhesion of the secondary gill lamellae associated with severe leukocytic infiltration. Furthermore, liver functions enzymes (aspartate aminotransferase and alanine aminotransferase, and the activities of glutathione peroxidase, glutathione reductase, lipid peroxidase, and catalase enzymes were significantly increased in all treatments starting from the 2nd week as compared to the control levels. Conclusion: In this context, the study addresses the possible toxicological impacts of toxic M. aeruginosa contain MC-LR to Nile tilapia, and the results investigated that MC-LR is toxic to Nile tilapia in different routes of exposure as well as different doses.

  1. Effects of sub-chronic exposure to SO{sub 2} on lipid and carbohydrate metabolism in rats

    Energy Technology Data Exchange (ETDEWEB)

    Lovati, M.R. [Institute of Pharmacological Sciences, Milan (Italy); Manzoni, C. [Institute of Pharmacological Sciences, Milan (Italy); Daldossi, M. [Institute of Pharmacological Sciences, Milan (Italy); Spolti, S. [Institute of Pharmacological Sciences, Milan (Italy); Sirtori, C.R. [Institute of Pharmacological Sciences, Milan (Italy)

    1996-01-01

    Sulfur dioxide (SO{sub 2}) is a ubiquitous air pollutant, present in low concentrations in the urban air, and in higher concentrations in the working environment. While toxicological reports on SO{sub 2} have extensively dealt with the pulmonary system, essentially no data are available on the effects of chronic exposure to this pollutant on intermediary metabolism, although some biochemical changes in lipid metabolism have been detected. The present investigation was aimed at evaluating the effects of sub-chronic exposure to SO{sub 2} on concentrations of serum lipids/lipoproteins and on glucose metabolism, in animal models of hypercholesterolemia and diabetes. A specially designed controlinert atmosphere chamber was used, where male Sprague-Dawley rats fed on either standard or cholesterol enriched (HC) diets, as well as streptozotocin diabetics, were exposed to SO{sub 2} at 5 and 10 ppm, 24 h per day for 14 days. In rats, both on a standard diet and on a HC regimen, SO{sub 2} exposure determined a significant dose-dependent increase in plasma triglycerides, up to +363% in the 10 ppm HC exposed animals. This same gas concentration significantly reduced HDL cholesterol levels. In contrast, exposure of diabetic animals to 10 ppm SO{sub 2} resulted in a fall (-41%) of plasma and liver triglycerides and in a concomitant increase (+62%) of plasma HDL cholesterol. This discrepancy could apparently be related to diverging effects of SO{sub 2} exposure on plasma insulin levels in the different animal groups. Kinetic analyses of triglyceride synthesis carried out in rats on a standard diet revealed, in exposed animals, a significant reduction in the secretory rate, in spite of the concomitant hypertriglyceridemia. These findings suggest that SO{sub 2} exposure can markedly modify major lipid and glycemic indices, also indicating a differential response in normo/hyperlipidemic versus diabetic animals. (orig.)

  2. Acute and subchronic toxicity of inhaled toluene in male Long Evans rats: oxidative stress markers in brain

    Data.gov (United States)

    U.S. Environmental Protection Agency — Research interested in oxidative stress markers following exposure to VOCs. This dataset is associated with the following publication: Kodavanti , P., J. Royland ,...

  3. Cancer and Toxicology Section

    International Nuclear Information System (INIS)

    Anon.

    1980-01-01

    The Cancer and Toxicology Section is concerned with the investigation of the mechanisms by which chemicals, radiation, and viruses cause the changes broadly identified as cancer. In addition, the study of mechanisms has been extended to include the nontumorigenic effects of various agents associated with fossil energy and fuels. Research in molecular genetics of carcinogenesis focuses largely on the transposon properties of the genomes of retroviruses. The transposon structure of the DNA genomes of endogenous murine N-tropic and B-tropic type C retroviruses is being elucidated, and their chromosomal location mapped in hamster-mouse cell hybrids. A model of the mechanism of retrovirus induction by radiation and chemicals is being developed, and experiments have established that compounds such as hydroxyurea act as inducer. There is the possibility that transposition of sequences of this endogenous virus may be linked to leukemogenesis. Research in regulation of gene expression aims at defining in molecular terms the mechanisms determining expression of specific genes, how these are regulated by hormones, and the events responsible for dysfunction of gene expression in cancer. In corollary work, a library of cloned cDNAs specific for products of genes of special interest to regulation is being developed. Improvement of reversed-phase chromatography as a means of isolating bacterial plasmids and restriction fragments of DNA is underway. Newly developed techniques permit the isolation of supercoiled plasmid DNA directly from bacterial extracts. The technology has been developed recently for the photosynthetic growth of the chemo-autotrophic organism Rhodospirillum rubrum and the enzyme ribulosebisphosphate carboxylase has been produced in quantity

  4. Inhaled plutonium nitrate in dogs

    International Nuclear Information System (INIS)

    Dagle, G.E.; Cannon, W.C.; Ragan, H.A.; Watson, C.R.; Stevens, D.L.; Cross, F.T.; Dionne, P.J.; Harrington, T.P.

    1978-01-01

    Beagle dogs given a single inhalation exposure to 239 Pu(NO 3 ) 4 are being observed for life-span dose-effect relationships. Lymphopenia occurred at the two highest dosage levels as early as 1 mo following exposure and was associated with neutropenia and reduction in numbers of circulatory monocytes by 4 mo postexposure. Radiation pneumonitis developed in one dog at the highest dosage level at 14 mo postexposure. More rapid translocation to skeleton and liver occurred following inhalation of 238 Pu(NO 3 ) 4 than after 239 Pu(NO 3 ) 4 inhalation

  5. The gut microbiota influence behavior in the subchronic PCP induced animal model of schizophrenia

    DEFF Research Database (Denmark)

    Jørgensen, Bettina Merete Pyndt; Redrobe, Paul; Brønnum Pedersen, Tina

    The gut microbiota has major impact on the individual. Here we show that the gut microbiota influence behavior in the subchronic PCP induced animal model of schizophrenia. The gut microbiota were changed in the group treated subchronic with PCP, and restoration coincided with normalisation...... of memory performance in lister hooded rats. Furthermore the individual gut microbiota correlated to the individual behavior abserved in the tests conducted. In conclusion results show an influence of the gut microbiota on behavior in this model, and therefore it might be relavant to include the information...

  6. KFK Institute of Genetics and of Toxicology of Fission Materials. 1990 annual report on research and development work

    International Nuclear Information System (INIS)

    1991-03-01

    The annual report summarizes the R+D activities of the Institute performed in the year 1990 in accordance with the Institute's R+D framework. The activities cover studies on gene repair, gene regulation, biological carcinogenesis, molecular genetics of enkaryontic genes, genetic mouse models for the study of human disease, radiotoxicology of the actinides, cellular inhalation toxicology, cellular and molecular toxicology, fractionation and speciation of actinides in vivo. There is a bibliography of publications issued by members of the Institute in 1990 and of the IGT primary reports issued in 1989 and 1990, and a list of lectures held but not available in printed form. (VHE) [de

  7. Inhaled Corticosteroids (ICSs) and Pregnancy

    Science.gov (United States)

    ... of the airways in the lungs and reduce mucus production so that asthma attacks are less likely. ... of medicine that would be in the breast milk following inhalation is likely too small to cause ...

  8. Toxicological aspects of energy production

    International Nuclear Information System (INIS)

    Sanders, C.L.

    1986-01-01

    Part I reviews the principles of toxicology, describes the biological fate of chemicals in the body, discusses basic pathobiology, and reviews short-term toxicity tests. Part II describes the toxicology and pathology of pollutants in several important organ systems. The greatest emphasis is placed on the respiratory tract because of its high probability as a route of exposure to pollutants from energy technologies and its high sensitivity to pollutant related tissue damage. Part III describes the toxicological aspects of specific chemical classes associated with fossil fuels; these include polycyclic hydrocarbons, gases and metals. Part IV describes the biomedical effects associated with each energy technology, including coal and oil, fossil fuel and biomass conversions, solar and geothermal and radiological health aspects associated with uranium mining, nuclear fission and fusion, and with nonionising radiations and electromagnetic fields

  9. 2007 TOXICOLOGY AND RISK ASSESSMENT ...

    Science.gov (United States)

    EPA has announced The 2007 Toxicology and Risk Assessment Conference Cincinnati Marriott North, West Chester (Cincinnati), OHApril 23- 26, 2007 - Click to register!The Annual Toxicology and Risk Assessment Conference is a unique meeting where several Government Agencies come together to discuss toxicology and risk assessment issues that are not only of concern to the government, but also to a broader audience including academia and industry. The theme of this year's conference is Emerging Issues and Challenges in Risk Assessment and the preliminary agenda includes: Plenary Sessions and prominent speakers (tentative) include: Issues of Emerging Chemical ContaminantsUncertainty and Variability in Risk Assessment Use of Mechanistic data in IARC evaluationsParallel Sessions:Uncertainty and Variability in Dose-Response Assessment Recent Advances in Toxicity and Risk Assessment of RDX The Use of Epidemiologic Data for Risk Assessment Applications Cumulative Health Risk Assessment:

  10. Inhaled plutonium oxide in dogs

    International Nuclear Information System (INIS)

    Anon.

    1981-01-01

    This project is concerned with long-term experiments to determine the life-span dose-effect relationships of inhaled 239 PuO 2 and 238 PuO 2 in beagles. The data will be used to estimate the health effects of inhaled transuranics. The tissue distribution of plutonium, radiation effects in the lung and hematologic changes in plutonium-exposed beagles with lung tumors were evaluated

  11. Respirable versus inhalable dust sampling

    International Nuclear Information System (INIS)

    Hondros, J.

    1987-01-01

    The ICRP uses a total inhalable dust figure as the basis of calculations on employee lung dose. This paper was written to look at one aspect of the Olympic Dam dust situation, namely, the inhalable versus respirable fraction of the dust cloud. The results of this study will determine whether it is possible to use respirable dust figures, as obtained during routine monitoring to help in the calculations of employee exposure to internal radioactive contaminants

  12. Proteomic analysis of rat cerebral cortex following subchronic acrolein toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Rashedinia, Marzieh; Lari, Parisa [Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of); Abnous, Khalil, E-mail: Abnouskh@mums.ac.r [Pharmaceutical Research Center, Department of Medicinal Chemistry, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of); Hosseinzadeh, Hossein, E-mail: Hosseinzadehh@mums.ac.ir [Pharmaceutical Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of)

    2013-10-01

    Acrolein, a member of reactive α,β-unsaturated aldehydes, is a major environmental pollutant. Acrolein is also produced endogenously as a toxic by-product of lipid peroxidation. Because of high reactivity, acrolein may mediate oxidative damages to cells and tissues. It has been shown to be involved in a wide variety of pathological states including pulmonary, atherosclerosis and neurodegenerative diseases. In this study we employed proteomics approach to investigate the effects of subchronic oral exposures to 3 mg/kg of acrolein on protein expression profile in the brain of rats. Moreover effects of acrolein on malondialdehyde (MDA) levels and reduced glutathione (GSH) content were investigated. Our results revealed that treatment with acrolein changed levels of several proteins in diverse physiological process including energy metabolism, cell communication and transport, response to stimulus and metabolic process. Interestingly, several differentially over-expressed proteins, including β-synuclein, enolase and calcineurin, are known to be associated with human neurodegenerative diseases. Changes in the levels of some proteins were confirmed by Western blot. Moreover, acrolein increases the level of MDA, as a lipid peroxidation biomarker and decreased GSH concentrations, as a non-enzyme antioxidant in the brain of acrolein treated rats. These findings suggested that acrolein induces the oxidative stress and lipid peroxidation in the brain, and so that may contribute to the pathophysiology of neurological disorders. - Highlights: • Acrolein intoxication increased lipid peroxidation and deplete GSH in rat brain. • Effect of acrolein on protein levels of cerebral cortex was analyzed by 2DE-PAGE. • Levels of a number of proteins with different biological functions were increased.

  13. Proteomic analysis of rat cerebral cortex following subchronic acrolein toxicity

    International Nuclear Information System (INIS)

    Rashedinia, Marzieh; Lari, Parisa; Abnous, Khalil; Hosseinzadeh, Hossein

    2013-01-01

    Acrolein, a member of reactive α,β-unsaturated aldehydes, is a major environmental pollutant. Acrolein is also produced endogenously as a toxic by-product of lipid peroxidation. Because of high reactivity, acrolein may mediate oxidative damages to cells and tissues. It has been shown to be involved in a wide variety of pathological states including pulmonary, atherosclerosis and neurodegenerative diseases. In this study we employed proteomics approach to investigate the effects of subchronic oral exposures to 3 mg/kg of acrolein on protein expression profile in the brain of rats. Moreover effects of acrolein on malondialdehyde (MDA) levels and reduced glutathione (GSH) content were investigated. Our results revealed that treatment with acrolein changed levels of several proteins in diverse physiological process including energy metabolism, cell communication and transport, response to stimulus and metabolic process. Interestingly, several differentially over-expressed proteins, including β-synuclein, enolase and calcineurin, are known to be associated with human neurodegenerative diseases. Changes in the levels of some proteins were confirmed by Western blot. Moreover, acrolein increases the level of MDA, as a lipid peroxidation biomarker and decreased GSH concentrations, as a non-enzyme antioxidant in the brain of acrolein treated rats. These findings suggested that acrolein induces the oxidative stress and lipid peroxidation in the brain, and so that may contribute to the pathophysiology of neurological disorders. - Highlights: • Acrolein intoxication increased lipid peroxidation and deplete GSH in rat brain. • Effect of acrolein on protein levels of cerebral cortex was analyzed by 2DE-PAGE. • Levels of a number of proteins with different biological functions were increased

  14. COMPARATIVE STUDY FOR SUBCHRONIC TOXICITY OF VASELINE OIL AND GLYCELAX

    Directory of Open Access Journals (Sweden)

    A. V. Voronkov

    2016-01-01

    Full Text Available Contemporary therapeutic approaches offer a wide range of laxative agents, which are often used without a control, exceeding the regime recommended. Therefore, the comparative study for subchronic toxicity of both drugs from this group (Vaseline oil and Glycelax appears interesting.The aim of the study was the comparison of a toxic influence of 14-days application of the drugs under study.Methods. The drugs were studied in two doses: higher therapeutic, and toxic, which 10 times exceeds therapeutic dose. We used “Polispektr-8/B” electrocardiograph, BC 2800vet (Mindray hematologic veterinary analyzer, BS-380 (Mindray biochemical analyzer, CL-50 urine analyzer. After the animals autopsy we determined organs’ coefficient (heart, lungs, spleen, liver, stomach, kidneys, adrenals.Results. While studying the ECG of female rats, amplitude of R wave increased after they got Glycelax in both doses. Female rats who got Vaseline oil this index decreased at minimum dose and increased at maximum dose. After Glycelax application, male rats had an increased activity of alanine aminotransferase. After Vaseline oil application at maximum dose, female rats had alkaline phosphatase activity lowered. Female rats, which got a maximum dose of Vaseline oil had a total protein lowered. Glycelax at maximum dose increased the content of bilirubin and its fractions in male and female rats, while Vaseline oil application at maximum dose increased the content of bilirubin in female rats. Male rats which got Glycelax had hemoglobin and hematocrit level increased.Conclusion. At long-term application of Vaseline oil, animals of both genders had heart disorders with possible development of arrhythmia, hepatotoxic effect, lipid exchange dysfunction. After excessive use of Glycelax the above mentioned is added with possible hemoglobin and rheological blood properties level decrease.

  15. Developmental and Reproductive Toxicology Database (DART)

    Data.gov (United States)

    U.S. Department of Health & Human Services — A bibliographic database on the National Library of Medicine's (NLM) Toxicology Data Network (TOXNET) with references to developmental and reproductive toxicology...

  16. IRIS Toxicological Review of Acrolein (2003 Final)

    Science.gov (United States)

    EPA announced the release of the final report, Toxicological Review of Acrolein: in support of the Integrated Risk Information System (IRIS). The updated Summary for Acrolein and accompanying toxicological review have been added to the IRIS Database.

  17. Toxicological evaluation of the flavour ingredient N-(1-((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yloxy-2-methylpropan-2-yl-2,6-dimethylisonicotinamide (S2218

    Directory of Open Access Journals (Sweden)

    Donald S. Karanewsky

    Full Text Available A toxicological evaluation of N-(1-((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yloxy-2-methylpropan-2-yl-2,6-dimethylisonicotinamide (S2218; CAS 1622458-34-7, a flavour with modifying properties, was completed for the purpose of assessing its safety for use in food and beverage applications. S2218 exhibited minimal oxidative metabolism in vitro, and in rat pharmacokinetic studies, the compound was poorly orally bioavailable and rapidly eliminated. S2218 was not found to be mutagenic in an in vitro bacterial reverse mutation assay, and was found to be neither clastogenic nor aneugenic in an in vitro mammalian cell micronucleus assay. In subchronic oral toxicity studies in male and female rats, the NOAEL was 140 mg/kg bw/day (highest dose tested for S2218 sulfate salt (S8069 when administered as a food ad-mix for 13 consecutive weeks. Furthermore, S2218 sulfate salt demonstrated a lack of maternal toxicity, as well as adverse effects on fetal morphology at the highest dose tested, providing a NOAEL of 1000 mg/kg bw/day for both maternal toxicity and embryo/fetal development when administered orally during gestation to pregnant rats. Keywords: Flavours with modifying properties, S2218, FEMA GRAS, Subchronic toxicological evaluation, Genetic toxicological evaluation, Developmental toxicity evaluation

  18. Effects of p-xylene inhalation on axonal transport in the rat retinal ganglion cells

    Energy Technology Data Exchange (ETDEWEB)

    Padilla, S.S.; Lyerly, D.P. (Environmental Protection Agency, Research Triangle Park, NC (USA))

    1989-12-01

    Although the solvent xylene is suspected of producing nervous system dysfunction in animals and humans, little is known regarding the neurochemical consequences of xylene inhalation. The intent of this study was to determine the effect of intermittent, acute, and subchronic p-xylene exposure on the axonal transport of proteins and glycoproteins within the rat retinofugal tract. A number of different exposure regimens were tested ranging from 50 ppm for a single 6-hr exposure to 1600 ppm 6 hr/day, 5 days/week, for a total of 8 exposure days. Immediately following removal from the inhalation chambers rats were injected intraocularly with (35S)methionine and (3H)fucose (to label retinal proteins and glycoproteins, respectively) and the axonal transport of labeled macromolecules to axons (optic nerve and optic tract) and nerve endings (lateral geniculate body and superior colliculus) was examined 20 hr after precursor injection. Only relatively severe exposure regimens (i.e., 800 or 1600 ppm 6 hr/day, 5 days/week, for 1.5 weeks) produced significant reductions in axonal transport; there was a moderate reduction in the axonal transport of 35S-labeled proteins in the 800-ppm-treated group which was more widespread in the 1600 ppm-treated group. Transport of 3H-labeled glycoproteins was less affected. Assessment of retinal metabolism immediately after isotope injection indicated that the rate of precursor uptake was not reduced in either treatment group. Furthermore, rapid transport was still substantially reduced in animals exposed to 1600 ppm p-xylene and allowed a 13-day withdrawal period. These data indicate that p-xylene inhalation decreases rapid axonal transport supplied to the projections of the rat retinal ganglion cells immediately after cessation of inhalation exposure and that this decreased transport is still apparent 13 days after the last exposure.

  19. Effects of p-xylene inhalation on axonal transport in the rat retinal ganglion cells

    International Nuclear Information System (INIS)

    Padilla, S.S.; Lyerly, D.P.

    1989-01-01

    Although the solvent xylene is suspected of producing nervous system dysfunction in animals and humans, little is known regarding the neurochemical consequences of xylene inhalation. The intent of this study was to determine the effect of intermittent, acute, and subchronic p-xylene exposure on the axonal transport of proteins and glycoproteins within the rat retinofugal tract. A number of different exposure regimens were tested ranging from 50 ppm for a single 6-hr exposure to 1600 ppm 6 hr/day, 5 days/week, for a total of 8 exposure days. Immediately following removal from the inhalation chambers rats were injected intraocularly with [35S]methionine and [3H]fucose (to label retinal proteins and glycoproteins, respectively) and the axonal transport of labeled macromolecules to axons (optic nerve and optic tract) and nerve endings (lateral geniculate body and superior colliculus) was examined 20 hr after precursor injection. Only relatively severe exposure regimens (i.e., 800 or 1600 ppm 6 hr/day, 5 days/week, for 1.5 weeks) produced significant reductions in axonal transport; there was a moderate reduction in the axonal transport of 35S-labeled proteins in the 800-ppm-treated group which was more widespread in the 1600 ppm-treated group. Transport of 3H-labeled glycoproteins was less affected. Assessment of retinal metabolism immediately after isotope injection indicated that the rate of precursor uptake was not reduced in either treatment group. Furthermore, rapid transport was still substantially reduced in animals exposed to 1600 ppm p-xylene and allowed a 13-day withdrawal period. These data indicate that p-xylene inhalation decreases rapid axonal transport supplied to the projections of the rat retinal ganglion cells immediately after cessation of inhalation exposure and that this decreased transport is still apparent 13 days after the last exposure

  20. 42 CFR 493.937 - Toxicology.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Toxicology. 493.937 Section 493.937 Public Health... Proficiency Testing Programs by Specialty and Subspecialty § 493.937 Toxicology. (a) Program content and frequency of challenge. To be approved for proficiency testing for toxicology, the annual program must...

  1. 42 CFR 493.1213 - Condition: Toxicology.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Toxicology. 493.1213 Section 493.1213 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES....1213 Condition: Toxicology. If the laboratory provides services in the subspecialty of Toxicology, the...

  2. Toxicological and radiological safety of chicken meat irradiated with 7.5 MeV X-rays

    Science.gov (United States)

    Song, Beom-Seok; Lee, Yunjong; Park, Jong-Heum; Kim, Jae-Kyung; Park, Ha-Young; Kim, Dong-Ho; Kim, Chang-Jong; Kang, Il-Jun

    2018-03-01

    This study was conducted to evaluate the toxicological and radiological safety of chicken meat that had been irradiated at 30 kGy with 7.5 MeV X-rays. In a sub-chronic toxicity study, ICR mice were fed X-ray-irradiated chicken meat at 2500 mg/kg body weight daily for 90 days, and no mortality or abnormal clinical signs were observed throughout the study period. However, several hematological and serum biochemical parameters of the ICR mice differed significantly from those in the control group; nevertheless, the observed values were all within the normal range for the respective parameters. In addition, no toxicological effects were determined in male or female mice. Furthermore, no differences in gamma-ray spectrometric patterns were detected between the non-irradiated and irradiated samples, indicating that the radioactivity induced by 7.5 MeV X-ray irradiation was below the detection limit. These results tentatively suggest that chicken meat irradiated with 7.5 MeV X-rays would be safe for human consumption in terms of toxicology and radiology.

  3. Toxicological Assessment of β-(1à6-Glucan (Lasiodiplodan in Mice during a 28-Day Feeding Study by Gavage

    Directory of Open Access Journals (Sweden)

    Janaína A. Túrmina

    2012-12-01

    Full Text Available Studies evaluating the toxicity caused by fungal exopolysaccharides of the β-(1®6-D-glucan type are rare. In this study, the toxicological effects of sub-chronic treatments with lasiodiplodan (β-(1®6-D-glucan from Lasiodiplodia theobromae MMPI were evaluated in mice through the assessment of biochemical, hematological, and histopathological alterations. Thirty-two mice (16 male, 16 female were used in this study divided in two groups; one group received lasiodiplodan (50 mg/kg body weight daily for 28 days via gavage, and another (control group received saline during the same period. Blood samples were collected via cardiac puncture for hematological and biochemical analyses. Liver, heart, kidney, and spleen were collected for histopathological analysis. Statistical analysis was performed through one-way analysis of variance and only p < 0.05 F-values were presented. Significant reduction in blood glucose in the male group (35%; p < 0.01, transaminases activity in both sexes (AST and ALT; ~35%; p < 0.05, and urea (20%; p < 0.01 in the female group was observed with the lasiodiplodan treatment. The results showed that sub-chronic treatments with lasiodiplodan did not generate hematological and histopathological alterations leading to signs of toxicity in healthy mice, independent of gender.

  4. Histopathological alterations of white seabass, Lates calcarifer, in acute and subchronic cadmium exposure

    Energy Technology Data Exchange (ETDEWEB)

    Thophon, S.; Kruatrachue, M.; Upatham, E.S.; Pokethitiyook, P.; Sahaphong, S.; Jaritkhuan, S

    2003-03-01

    White seabass responded differently to cadmium at chronic and subchronic levels. - Histopathological alterations to white seabass, Lates calcarifer aged 3 months in acute and subchronic cadmium exposure were studied by light and scanning electron microscopy. The 96-h LC{sub 50} values of cadmium to L. calcarifer was found to be 20.12{+-}0.61 mg/l and the maximum acceptable toxicant concentration (MATC) was 7.79 mg/l. Fish were exposed to 10 and 0.8 mg/l of Cd (as CdCl{sub 2}H{sub 2}O) for 96 h and 90 days, respectively. The study showed that gill lamellae and kidney tubules were the primary target organs for the acute toxic effect of cadmium while in the subchronic exposure, the toxic effect to gills was less than that of kidney and liver. Gill alterations included edema of the epithelial cells with the breakdown of pillar cell system, aneurisms with some ruptures, hypertrophy and hyperplasia of epithelial and chloride cells. The liver showed blood congestion in sinusoids and hydropic swelling of hepatocytes, vacuolation and dark granule accumulation. Lipid droplets and glycogen content were observed in hepatocytes at the second and third month of subchronic exposure. The kidney showed hydropic swelling of tubular cell vacuolation and numerous dark granule accumulation in many tubules. Tubular degeneration and necrosis were seen in some areas.

  5. Acute and sub-chronic oral toxicity studies of methanol extract of ...

    African Journals Online (AJOL)

    Acute and sub-chronic oral toxicity studies of methanol extract of Clinacanthus nutans in mice. Zainul Amiruddin Zakaria, Mohammad Hafiz Abdul Rahim, Norhafizah Mohtarrudin, Arifah Abdul Kadir, Manraj Singh Cheema, Zuraini Ahmad, Ching Siew Mooi, Siti Farah Md. Tohid ...

  6. Safety assessment of hydroethanolic rambutan rind extract: acute and sub-chronic toxicity studies.

    Science.gov (United States)

    Thinkratok, Aree; Suwannaprapha, Parin; Srisawat, Rungrudee

    2014-10-01

    This study evaluated the safety of rambutan rind extract (RRE) in male Wistar rats. While acute toxicity was evaluated by feeding the rats with single doses of RRE (1000, 2000, 3000, 4000, and 5000 mg/kg) and its sub-chronic toxicity was observed in rats orally administered with RRE (500, 1000, and 2000 mg/kg) daily for 30 days. In acute toxicity study, the LD50 was found to be greater than 5000 mg/kg of RRE. In sub-chronic toxicity study, no mortality and sign of toxicity was found up to 1000 mg/kg/day of RRE. At 2000 mg/kg/day dose, the mortality rate was 12.5%. Significant decreases in body weight gain and food consumption were found in both acute and sub-chronic toxicity studies. In acute toxicity study, all the studied doses of RRE did not alter serum levels of triglyceride (TG), aspartate aminotransferase (AST) andalanine aminotransferase (ALT). In sub-chronic toxicity study, all studied doses of RRE significantly decreased plasma levels of TG and blood urea nitrogen, but did not alter plasma levels of AST and ALT. TC levels did not show any significant change in both the studies. The obtained results provide basic information for in vivo experimental studies of the pharmacological potentiality of RRE.

  7. Acute and Sub-chronic (28-day) Oral Toxicity Studies of ...

    African Journals Online (AJOL)

    Erah

    was to investigate the acute and sub-chronic toxicity of A. conyzoides leaves in Wistar rats. Methods: In the acute test, the ... associated with navel in children [4], and in the treatment of ... Ethical Committee for Teaching and. Research (ref no.

  8. Acute and subchronic airway inflammation after intratracheal instillation of quartz and titanium dioxide agglomerates in mice

    DEFF Research Database (Denmark)

    Roursgaard, Martin; Jensen, Keld A; Poulsen, Steen Seier

    2011-01-01

    This study investigated the acute and subchronic inflammatory effects of micrometer-size (micro-size) and nanometer-size (nano-size) particles after intratracheal (i.t.) installation in mice. The role of the type of compound, polymorphism, and size of the particles was investigated. Studied compo...

  9. Inhaled Drug Delivery: A Practical Guide to Prescribing Inhaler Devices

    Directory of Open Access Journals (Sweden)

    Pierre Ernst

    1998-01-01

    Full Text Available Direct delivery of medication to the target organ results in a high ratio of local to systemic bioavailability and has made aerosol delivery of respiratory medication the route of choice for the treatment of obstructive lung diseases. The most commonly prescribed device is the pressurized metered dose inhaler (pMDI; its major drawback is the requirement that inspiration and actuation of the device be well coordinated. Other requirements for effective drug delivery include an optimal inspiratory flow, a full inspiration from functional residual capacity and a breath hold of at least 6 s. Available pMDIs are to be gradually phased out due to their use of atmospheric ozone-depleting chlorofluorocarbons (CFCs as propellants. Newer pMDI devices using non-CFC propellants are available; preliminary experience suggests these devices greatly increase systemic bioavailability of inhaled corticosteroids. The newer multidose dry powder inhalation devices (DPIs are breath actuated, thus facilitating coordination with inspiration, and contain fewer ingredients. Furthermore, drug delivery is adequate even at low inspired flows, making their use appropriate in almost all situations. Equivalence of dosing among different devices for inhaled corticosteroids will remain imprecise, requiring the physician to adjust the dose of medication to the lowest dose that provides adequate control of asthma. Asthma education will be needed to instruct patients on the effective use of the numerous inhalation devices available.

  10. Surprises and omissions in toxicology

    Czech Academy of Sciences Publication Activity Database

    Rašková, H.; Zídek, Zdeněk

    2004-01-01

    Roč. 12, - (2004), S94-S96 ISSN 1210-7778. [Inderdisciplinary Czech-Slovak Toxicological Conference /8./. Praha, 03.09.2004-05.09.2004] Institutional research plan: CEZ:AV0Z5008914 Keywords : bacterial toxins Subject RIV: FR - Pharmacology ; Medidal Chemistry

  11. Subchronic and chronic toxicity of ingested 1,3-dichloropropene in dogs.

    Science.gov (United States)

    Stebbins, K E; Quast, J F; Haut, K T; Stott, W T

    1999-12-01

    The potential toxicologic effects to dogs of 1,3-dichloropropene (1, 3-D), a soil fumigant used for the control of nematodes, were investigated. The 13-week subchronic toxicity study consisted of male and female beagle dogs (4/sex/dose group) given approximately 0, 5, 15, or 41 mg 1,3-D/kg body wt/day (approximately equivalent amounts of cis and trans isomers) via their diets. The 1-year chronic toxicity study consisted of male and female beagle dogs (4/sex/dose group) provided diets delivering approximately 0, 0.5, 2. 5, or 15 mg/kg body wt/day. The test material was stabilized in the feed by microencapsulation in a starch/sucrose matrix (80/20). In both the 13-week and the 1-year studies, the primary effect of 1,3-D in male and female dogs ingesting a dosage of >/=15 mg/kg/day was hypochromic, microcytic anemia. The anemia was regenerative, with increased erythropoietic activity characterized by polychromasia of erythrocytes and increased numbers of reticulocytes in peripheral blood. In the 13-week study, the anemia in dogs given 41 mg/kg/day progressively worsened over time, while the anemia in dogs given 15 mg/kg/day remained relatively constant between 42 and 90 days of dosing. Partial reversal of the anemia of high-dose animals occurred during a 5-week recovery period following the 13-week dosing regimen. In the 13-week study, terminal fasted body weights of males given 15 or 41 mg/kg/day were decreased 3 and 28%, respectively, and body weights of females given 5, 15, or 41 mg/kg/day were decreased 4.5, 12, and 24%, respectively, relative to controls. Males given 5 mg/kg/day for 13 weeks had no change in body weights relative to controls. In the 1-year study, the hypochromic microcytic anemia in dogs given 15 mg/kg/day remained relatively constant in severity between 3 and 12 months of treatment. Histopathologic alterations associated with anemia in the 1-year study consisted of increased hematopoiesis of the bone marrow and increased extramedullary

  12. Regulatory issues in accreditation of toxicology laboratories.

    Science.gov (United States)

    Bissell, Michael G

    2012-09-01

    Clinical toxicology laboratories and forensic toxicology laboratories operate in a highly regulated environment. This article outlines major US legal/regulatory issues and requirements relevant to accreditation of toxicology laboratories (state and local regulations are not covered in any depth). The most fundamental regulatory distinction involves the purposes for which the laboratory operates: clinical versus nonclinical. The applicable regulations and the requirements and options for operations depend most basically on this consideration, with clinical toxicology laboratories being directly subject to federal law including mandated options for accreditation and forensic toxicology laboratories being subject to degrees of voluntary or state government–required accreditation.

  13. Sub-chronic dietary toxicity of potassium perfluorooctanesulfonate in rats

    International Nuclear Information System (INIS)

    Seacat, Andrew M.; Thomford, Peter J.; Hansen, Kris J.; Clemen, Lisa A.; Eldridge, Sandra R.; Elcombe, Cliff R.; Butenhoff, John L.

    2003-01-01

    Perfluorooctanesulfonate (PFOS) is a widely disseminated persistent compound found at low (part-per-billion) concentrations in serum and liver samples from humans and fish-eating wildlife. This study investigated the hypotheses that early hepatocellular peroxisomal proliferation and hepatic cellular proliferation are factors in chronic liver response to dietary dosing, that lowering of serum total cholesterol is an early clinical measure of response to treatment, and that liver and serum PFOS concentrations are proportional to dose and cumulative dose after sub-chronic treatment. PFOS was administered in diet as the potassium salt at 0, 0.5, 2.0, 5.0, and 20 parts per million (ppm) to Sprague Dawley rats for 4 or 14 weeks. At 4 weeks, effects included decreased serum glucose and an equivocal (< twofold) increase in hepatic palmitoyl CoA oxidase (PCoAO) activity in 20 ppm dose-group males and elevation of alanine aminotransferase (ALT) in 20 ppm dose-group females. At 14 weeks, the 20 ppm males had increased liver weight, decreased serum cholesterol, increased non-segmented neutrophils, and increased ALT. Relative liver weights and urea nitrogen were increased in both sexes at 14 weeks. Hepatocytic hypertrophy and cytoplasmic vacuolation were observed in the 5 or 20 ppm male and the 20 ppm female dose groups. An increase in hepatic PCoAO activity was not observed at 14 weeks, and the average hepatocyte proliferation index was not increased, although, individual animals had mild increases. Serum and liver PFOS concentrations were proportional to dose and cumulative dose. Serum concentrations were generally higher in females than in males. The liver-to-serum PFOS ratios ranged from approximately 3:1 to 12:1. After 14 weeks, the no-observed-adverse effect level (NOAEL) in males and females was 5 ppm. The NOAEL corresponded to mean serum PFOS concentrations of 44 ppm (μg/ml) in males and 64 ppm in females and mean liver PFOS concentrations of 358 ppm in males and 370

  14. Toxicology of thorium cycle nuclides

    International Nuclear Information System (INIS)

    Ballou, J.E.

    1984-01-01

    The purpose of this project is to investigate the biological hazards associated with uranium-thorium breeder fuels and fuel recycle process solutions. Initial studies emphasize the metabolism and long-term biological effects of inhaled 233 U- 232 U nitrate and oxide fuel materials and of 231 Pa, a major, long-lived, radioactive waste product. 1 figure, 3 tables

  15. Synthetic vitreous fibers: a review toxicology, epidemiology and regulations.

    Science.gov (United States)

    Bernstein, David M

    2007-01-01

    This review addresses the characteristics which differentiate synthetic vitreous fibers (SVFs, e.g., fiber glass, stonewool, slagwool, refractory ceramic fibers, etc.), how these influence the potential biopersistence and toxicity, the most recent epidemiological results and the integration of these findings into the health and safety regulations in Europe and the United States. Also presented is the historical basis for the European classification directive. The use and equivalence of the chronic inhalation toxicology and chronic intraperitoneal injection studies in laboratory rodents for evaluation of fiber toxicology is assessed as well as the impact of dose selection and design on the validity of the study. While synthetic vitreous fibers can span a wide range of chemistries, recognition and understanding of the importance of biopersistence (ability to persist in the lung) in fiber toxicity has led to the development of more and more biosoluble fibers (that break down rapidly in the lung). Still, the epidemiological data available which are largely based upon the use of fibers in past decades, indicate that the SVF do not present a human health risk at current exposure levels. The animal toxicology and biopersistence data provide a coherent basis for understanding and evaluating the parameters which affect SVF toxicity. The current regulations are based upon an extensive knowledge base of chronic studies in laboratory rodents which confirm the relationship between chronic adverse effects and the biopersistence of the longer fibers that can not be fully phagocytised and efficiently cleared from the lung. The amorphous structure of synthetic vitreous fibers facilitates designing fibers in use today with low biopersistence. Both the epidemiological data and the animal studies database provide strong assurance that there is little if any health risk associated with the use of SVFs of low biopersistence. IARC (2001) reclassified these fibers from Category 2b to

  16. Compared biokinetic and biological studies of chronic and acute inhalations of uranium compounds in the rat

    International Nuclear Information System (INIS)

    Monleau, M.

    2005-12-01

    Uranium is a natural, radioactive heavy metal, widely used in the nuclear industry in various chemical and isotopic forms. Its use in the fuel cycle involves the risk of radiological exposure for the workers, mainly via the inhalation of uranium particles. According to the workplace configuration, uranium contaminations can be acute or repeated, involve various chemical forms and different levels of enrichment, as well as involving one or several components. The dosimetric concepts and models available for workers' radiological protection, as well as most of the studies of the biological effects, correspond to acute exposure situations. Moreover the processes leading to pathological effects are little known in vivo. In this context, the main question is to know whether exposures due to repeated inhalation by rats induce the element kinetics and toxicity, which may be different from those observed after an acute exposure. In this study, comparison of the experimental and theoretical biokinetics of an insoluble uranium repeatedly inhaled over three weeks shows that a chronic contamination is correctly modelled, except for bone retention, by the sum of acute, successive and independent incorporations. Moreover, the kinetics of a soluble uranium inhaled irregularly can be modified by previous repeated exposure to an insoluble uranium. In certain cases therefore, exposure to uranium could modify its biokinetics during later exposures. At a toxicological level, the study demonstrates that the uranium particles inhaled repeatedly induce behavioural disruptions and genotoxic effects resulting in various sorts of DNA damage, in several cell types and certainly depending on the quantity inhaled. Exposures involving several uraniferous components produce a synergy effect. Moreover, repeated inhalations worsen the genotoxic effects in comparison to an acute exposure. This work demonstrates the importance of not ignoring the effects of the repetition of uranium exposure. It

  17. Computational Fluid Dynamics Simulations of Inhaled Nano-and Micro-Particle Deposition in the Rhesus Monkey Nasal Passages

    Science.gov (United States)

    2016-12-01

    reconstruction of the adult model was originally developed by Kepler et al. (1998) from serial Magnetic Resonance Imaging ( MRI ) sections of the right...upper airways and MRI imaging of a lung cast to form a contiguous reconstruction from the nostrils through 19 airway generations of the lung. For this...and Musante, C. J. (2001). A nonhuman primate aerosol deposition model for toxicological and pharmaceutical studies. Inhal. Toxicol. 13:307-324

  18. Inhaled plutonium nitrate in dogs

    International Nuclear Information System (INIS)

    Dagle, G.E.

    1987-01-01

    The major objective of this project is to determine dose-effect relationships of inhaled plutonium nitrate in dogs to aid in predicting health effects of accidental exposure in man. For lifespan dose-effect studies, beagle dogs were given a single inhalation exposure to 239 Pu(NO 3 ) 4 , in 1976 and 1977. The earliest biological effect was on the hematopoietic system; lymphopenia and neutropenia occurred at the two highest dose levels. They have also observed radiation pneumonitis, lung cancer, and bone cancer at the three highest dose levels. 1 figure, 3 tables

  19. Inhaled plutonium nitrate in dogs

    International Nuclear Information System (INIS)

    Dagle, G.E.

    1986-01-01

    The major objective of this project is to determine dose-effect relationships of inhaled plutonium nitrate in dogs to aid in predicting health effects of accidental exposure in man. For lifespan dose-effect studies, beagle dogs were given a single inhalation exposure to 239 Pu(NO 3 ) 4 , in 1976 and 1977. The earliest biological effect was on the hematopoietic system; lymphopenia and neutropenia occurred at the two highest dose levels. The authors have also observed radiation pneumonitis, lung cancer, and bone cancer at the three highest dose levels. 1 figure, 4 tables

  20. Inhaled plutonium nitrate in dogs

    International Nuclear Information System (INIS)

    Dagle, G.E.

    1982-01-01

    The major objective of this project is to determine dose-effect relationships of inhaled plutonium nitrate in dogs to aid in the prediction of health effects of accidental exposure in man. For lifespan dose-effect studies, beagle dogs were given a single inhalation exposure to 239 Pu(NO 3 ) 4 , in 1976 and 1977. The earliest biological effect was on the hematopoietic system; as described in previous Annual Reports, lymphopenia and neutropenia occurred at the two highest dose levels. Radiation pneumonitis, lung cancer, and bone cancer have been observed at the highest dose levels

  1. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... for Control Triggers Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers Data, Statistics, ... How to Use Your Asthma Inhaler Recommend on Facebook Tweet Share Compartir You can control your asthma ...

  2. Electrostatic Properties of Particles for Inhalation

    OpenAIRE

    Rowland, Martin

    2015-01-01

    Dry powder inhalers (DPIs) and pressurised metered dose inhalers (pMDIs) aredevices used to deliver therapeutic agents to the lungs. Typically, inhaled activepharmaceutical ingredients (APIs) are electrically resistive materials and are prone toaccumulating electrostatic charge. The build-up of charge on inhaled therapeutics hastraditionally been viewed as a nuisance as it may result in problems such as weighingerrors, agglomeration, adhesion to surfaces and poor flow. Energetic processing st...

  3. Inhalation Injury: State of the Science 2016.

    Science.gov (United States)

    Foster, Kevin N; Holmes, James H

    This article summarizes research conducted over the last decade in the field of inhalation injury in thermally injured patients. This includes brief summaries of the findings of the 2006 State of the Science meeting with regard to inhalation injury, and of the subsequent 2007 Inhalation Injury Consensus Conference. The reviewed studies are categorized in to five general areas: diagnosis and grading; mechanical ventilation; systemic and inhalation therapy; mechanistic alterations; and outcomes.

  4. Safety and Toxicology of Cannabinoids

    OpenAIRE

    Sachs, Jane; McGlade, Erin; Yurgelun-Todd, Deborah

    2015-01-01

    There is extensive research on the safety, toxicology, potency, and therapeutic potential of cannabis. However, uncertainty remains facilitating continued debate on medical and recreational cannabis policies at the state and federal levels. This review will include a brief description of cannabinoids and the endocannabinoid system; a summary of the acute and long-term effects of cannabis; and a discussion of the therapeutic potential of cannabis. The conclusions about safety and efficacy will...

  5. Age dependent systemic exposure to inhaled salbutamol

    DEFF Research Database (Denmark)

    Bønnelykke, Klaus; Jespersen, Jakob Jessing; Bisgaard, Hans

    2007-01-01

    AIMS: To determine the effect of age on systemic exposure to inhaled salbutamol in children. METHODS: Fifty-eight asthmatic children, aged 3-16 years, inhaled 400 microg of salbutamol from a pressurized metered dose inhaler with spacer. The 20 min serum profile was analyzed. RESULTS: Prescribing...

  6. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... metered dose inhaler with a spacer [ PDF – 377 KB] Your browser does not support iframes Cómo usar ... inhalador de dosis fija con espaciador [PDF – 343 KB] Using a metered dose inhaler (inhaler in mouth) ...

  7. Estimation of inhalation flow profile using audio-based methods to assess inhaler medication adherence

    Science.gov (United States)

    Lacalle Muls, Helena; Costello, Richard W.; Reilly, Richard B.

    2018-01-01

    Asthma and chronic obstructive pulmonary disease (COPD) patients are required to inhale forcefully and deeply to receive medication when using a dry powder inhaler (DPI). There is a clinical need to objectively monitor the inhalation flow profile of DPIs in order to remotely monitor patient inhalation technique. Audio-based methods have been previously employed to accurately estimate flow parameters such as the peak inspiratory flow rate of inhalations, however, these methods required multiple calibration inhalation audio recordings. In this study, an audio-based method is presented that accurately estimates inhalation flow profile using only one calibration inhalation audio recording. Twenty healthy participants were asked to perform 15 inhalations through a placebo Ellipta™ DPI at a range of inspiratory flow rates. Inhalation flow signals were recorded using a pneumotachograph spirometer while inhalation audio signals were recorded simultaneously using the Inhaler Compliance Assessment device attached to the inhaler. The acoustic (amplitude) envelope was estimated from each inhalation audio signal. Using only one recording, linear and power law regression models were employed to determine which model best described the relationship between the inhalation acoustic envelope and flow signal. Each model was then employed to estimate the flow signals of the remaining 14 inhalation audio recordings. This process repeated until each of the 15 recordings were employed to calibrate single models while testing on the remaining 14 recordings. It was observed that power law models generated the highest average flow estimation accuracy across all participants (90.89±0.9% for power law models and 76.63±2.38% for linear models). The method also generated sufficient accuracy in estimating inhalation parameters such as peak inspiratory flow rate and inspiratory capacity within the presence of noise. Estimating inhaler inhalation flow profiles using audio based methods may be

  8. 21 CFR 862.3200 - Clinical toxicology calibrator.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Clinical toxicology calibrator. 862.3200 Section... (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3200 Clinical toxicology calibrator. (a) Identification. A clinical toxicology calibrator is...

  9. Resource Guide to Careers in Toxicology, 3rd Edition.

    Science.gov (United States)

    Society of Toxicology, Reston, VA.

    This resource guide was prepared by the Tox 90's Educational Issues Task Force of the Society of Toxicology. The introduction provides information on the Society of Toxicology and financial support for graduate students in toxicology. Other sections include career opportunities in toxicology, academic and postdoctoral programs in toxicology, and…

  10. Postmortem aviation forensic toxicology: an overview.

    Science.gov (United States)

    Chaturvedi, Arvind K

    2010-05-01

    An overview of the subtopic aviation combustion toxicology of the field of aerospace toxicology has been published. In a continuation of the overview, the findings associated with postmortem aviation forensic toxicology are being summarized in the present overview. A literature search for the period of 1960-2007 was performed. The important findings related to postmortem toxicology were evaluated. In addition to a brief introduction, this overview is divided into the sections of analytical methods; carboxyhemoglobin and blood cyanide ion; ethanol; drugs; result interpretation; glucose and hemoglobin A(1c); and references. Specific details of the subject matter were discussed. It is anticipated that this overview will be an outline source for aviation forensic toxicology within the field of aerospace toxicology.

  11. [Subchronic toxicity test of genetically modified rice with double antisense starch-branching enzyme gene].

    Science.gov (United States)

    Li, Min; Piao, Jianhua; Yang, Xiaoguang

    2010-07-01

    To observe the sub-chronic toxic effects of the genetically modified rice with double antisense SBE gene. Based on gender and weight, weanling Wistar rats were randomly sorted into five groups: non-genetically modified rice group (group A), genetically modified rice group (group B), half genetically modified rice group (group C), quarter genetically modified rice group (group D) and AIN-93G normal diet group (group E). Indicators were the followings: body weight, food consumption, blood routine, blood biochemical test, organ weight, bone density and pathological examination of organs. At the middle of the experiment, the percentage of monocyte of female group B was less than that of group E (P 0.05), and no notable abnormity in the pathological examination of main organs (P > 0.05). There were no enough evidence to confirm the sub-chronic toxicity of genetically modified rice on rats.

  12. Precipitated withdrawal counters the adverse effects of subchronic cannabinoid administration on male rat sexual behavior.

    Science.gov (United States)

    Riebe, Caitlin J; Lee, Tiffany T; Hill, Matthew N; Gorzalka, Boris B

    2010-03-26

    In the present study, sexual behavior of male rats was assessed following prolonged treatment with the CB(1) receptor agonist, HU-210 (0.1mg/mg/day for 10 days) under conditions of drug maintenance, spontaneous withdrawal and precipitated withdrawal (induced via administration of the CB(1) receptor antagonist AM251; 1mg/kg). Following subchronic cannabinoid treatment, sexual activity in male rats was impaired under both the drug maintenance and spontaneous withdrawal conditions, as revealed by a reduction in frequency of both intromissions and ejaculations. Notably, the induction of precipitated drug withdrawal reversed the negative effects of subchronic HU-210 treatment on sexual activity as seen by a reversal of the suppression of ejaculations. These data illustrate that, contrary to expectations, the impairments in male sexual activity following protracted cannabinoid administration are not due to drug withdrawal, per se, but are likely mediated by neuroadaptive changes provoked by repeated drug exposure. 2010 Elsevier Ireland Ltd. All rights reserved.

  13. History of Japanese Society of Toxicology.

    Science.gov (United States)

    Satoh, Tetsuo

    2016-01-01

    Founded in 1981, the Japanese Society of Toxicology (JSOT) has grown into an organization of nearly 3,000 members working together to advance the nation's scientific knowledge and understanding of toxicology through the implementation of planning that ensures a systematic and efficient expenditure of energies and resources, and is closely aligned with a strategy for accomplishing the Society's long-range plans. To promote public education in toxicology, the Society organizes public lectures during each year's annual meeting. Other activities include hosting scientific conferences, promoting continuing education, and facilitating international collaboration. Internally, the JSOT operates five standing committees: General Affairs, Educational, Editorial, Finance, and Science and Publicity to handle its necessary relationships. To bestow official recognition, the Society established its Toxicologist Certification Program in 1997, and has certified 536 members as Diplomat Toxicologists (DJSOT) as of May 1, 2016. Furthermore, on the same date, 43 JSOT members were certified as Emeritus Diplomats of the JSOT (EDJSOT). The Society has launched two official journals, the "Journal of Toxicological Sciences (JTS)" in 1981 and "Fundamental Toxicological Sciences (Fundam. Toxicol. Sci.)" in 2014. As for participation in the international organizations, the JSOT (then known as the Toxicological Research Group) joined the International Union of Toxicology as a charter member in 1980, and became a founding member of the Asian Society of Toxicology at its inauguration in 1994. Into the future, the JSOT will continue working diligently to advance knowledge and understanding of toxicology and secure its place among the interdisciplinary fields of science, humane studies, and ethics.

  14. Nephroprotective effect of bee honey and royal jelly against subchronic cisplatin toxicity in rats

    OpenAIRE

    Ibrahim, Abdelazim; Eldaim, Mabrouk A. Abd; Abdel-Daim, Mohamed M.

    2015-01-01

    Cisplatin is one of the most potent and effective chemotherapeutic agents. However, its antineoplastic use is limited due to its cumulative nephrotoxic side effects. Therefore, the present study was undertaken to examine the nephroprotective potential of dietary bee honey and royal jelly against subchronic cisplatin toxicity in rats. Male Wistar rats were randomly divided into controls, cisplatin-treated, bee honey-pretreated cisplatin-treated and royal jelly-pretreated cisplatin-treated grou...

  15. 78 FR 45253 - National Toxicology Program Scientific Advisory Committee on Alternative Toxicological Methods...

    Science.gov (United States)

    2013-07-26

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Toxicology Program... Alternative Methods (ICCVAM), the National Toxicology Program (NTP) Interagency Center for the Evaluation of... Director, National Toxicology Program. [FR Doc. 2013-17919 Filed 7-25-13; 8:45 am] BILLING CODE 4140-01-P ...

  16. Lifetime tumor risk coefficients for beagle dogs that inhaled cerium-144 chloride

    Energy Technology Data Exchange (ETDEWEB)

    Boecker, B.B.; Hahn, F.F.; Griffith, W.C. [and others

    1995-12-01

    Reported here is one of the life-span radionuclide toxicology studies being conducted at ITRI in Beagle dogs. These studies are examining the life-span health risks of inhaled {Beta}-, {gamma}- and {alpha}-emitting radionuclides to expand available knowledge on these risks especially for the many cases for which human data are not available. The outcomes of these studies are providing important information on dosimetry and dose-response relationships for these inhaled radionuclides and the relative importance of a broad range of dose- and effect-modifying factors. A number of these studies are currently coming to completion. Much of the ITRI effort is being directed to final reviews of the dosimetric, clinical, and pathologic results and writing summary manuscripts. Radiation doses and effects in tissues adjacent to bone, specifically those of epithelial or marrow origin, should be considered when determining risks from internally deposited, bone-seeking radionuclides such as {sup 144}Ce.

  17. Lifetime tumor risk coefficients for beagle dogs that inhaled cerium-144 chloride

    International Nuclear Information System (INIS)

    Boecker, B.B.; Hahn, F.F.; Griffith, W.C.

    1995-01-01

    Reported here is one of the life-span radionuclide toxicology studies being conducted at ITRI in Beagle dogs. These studies are examining the life-span health risks of inhaled Β-, γ- and α-emitting radionuclides to expand available knowledge on these risks especially for the many cases for which human data are not available. The outcomes of these studies are providing important information on dosimetry and dose-response relationships for these inhaled radionuclides and the relative importance of a broad range of dose- and effect-modifying factors. A number of these studies are currently coming to completion. Much of the ITRI effort is being directed to final reviews of the dosimetric, clinical, and pathologic results and writing summary manuscripts. Radiation doses and effects in tissues adjacent to bone, specifically those of epithelial or marrow origin, should be considered when determining risks from internally deposited, bone-seeking radionuclides such as 144 Ce

  18. Suicidal nitrogen inhalation by use of scuba full-face diving mask.

    Science.gov (United States)

    Straka, Lubomir; Novomesky, Frantisek; Gavel, Anton; Mlynar, Juraj; Hejna, Petr

    2013-09-01

    A 29-year-old man was found dead lying on the bed in a hotel room in a famous Slovak mountain resort. He had a full-face diving mask on his face, connected through a diving breath regulator to a valve of an industrial (nondiving) high-pressure tank containing pure 100% nitrogen. The breath regulator (open-circuit type) used allowed inhalation of nitrogen without addition of open air, and the full-face diving mask assured aspiration of the gas even during the time of unconsciousness. At autopsy, we found the typical signs of suffocation. Toxicological analysis revealed 94.7% content of nitrogen in alveolar air. Following the completion of the police investigation, the manner of death was classified as a suicide. Within the medico-legal literature, there has been only one similar case of suicidal nitrogen inhalation described. © 2013 American Academy of Forensic Sciences.

  19. Subchronic Toxicity Study of Standardized Methanolic Extract of Mitragyna Speciosa Korth in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Mohd Ulul Ilmie Ahmad Nazri

    2015-06-01

    Full Text Available Mitragyna speciosa Korth, or better known as ketum, has long been used by traditional folk around Southeast Asia to prevent fatigue from working under hot tropical weather and as a replacement of opium, which can then cause addiction. To date, no findings have been reported of the toxic effect of ketum subchronically (28 days. Hence, the aim of this study was to investigate the toxicity of subchronic effect of standardised methanolic extract of ketum (SMEMS in Sprague-Dawley rats. Rats were orally administered with 100, 200, and 500 mg/kg of SMEMS for 28 days. Body weights were recorded daily. They were terminated at day 28 to obtain data for haematology, biochemistry, and histopathology of the brain, liver, kidney, lung, heart, sciatic nerve, and spinal cord. The SMEMS affected body weight compared to control group. Biochemistry findings showed that liver and kidney were affected with the abnormal values in AST, creatinine, globulin, glucose, total protein, and urea. However, SMEMS produced toxic effect more to liver, kidney, and lung than other organs as observed histopathologically. The results suggested subchronic exposure of ketum is toxic to the physiology of the animals.

  20. Sub-chronic toxicity of low concentrations of industrial volatile organic pollutants in vitro

    International Nuclear Information System (INIS)

    McDermott, Catherine; Allshire, Ashley; Pelt, Frank N.A.M. van; Heffron, James J.A.

    2007-01-01

    Organic solvents form an important class of pollutants in the ambient air and have been associated with neurotoxicity and immunotoxicity in humans. Here we investigated the biological effects of sub-chronic exposure to industrially important volatile organic solvents in vitro. Jurkat T cells were exposed to toluene, n-hexane and methyl ethyl ketone (MEK) individually for 5 days and solvent exposure levels were confirmed by headspace gas chromatography. A neuroblastoma cell line (SH-SY5Y) was exposed to toluene for the same period. Following exposure, cells were harvested and toxicity measured in terms of the following endpoints: membrane damage (LDH leakage), perturbations in intracellular free Ca 2+ , changes in glutathione redox status and dual-phosphorylation of MAP kinases ERK1/2, JNK and p38. The results show that sub-chronic exposure to the volatile organic solvents causes membrane damage, increased intracellular free calcium and altered glutathione redox status in both cell lines. However, acute and sub-chronic solvent exposure did not result in MAP kinase phosphorylation. Toxicity of the solvents tested increased with hydrophobicity. The lowest-observed-adverse-effect-levels (LOAELs) measured in vitro were close to blood solvent concentrations reported for individuals exposed to the agents at levels at or below their individual threshold limit values (TLVs)

  1. Inhalation toxicity of indoor air pollutants in Drosophila melanogaster using integrated transcriptomics and computational behavior analyses

    Science.gov (United States)

    Eom, Hyun-Jeong; Liu, Yuedan; Kwak, Gyu-Suk; Heo, Muyoung; Song, Kyung Seuk; Chung, Yun Doo; Chon, Tae-Soo; Choi, Jinhee

    2017-06-01

    We conducted an inhalation toxicity test on the alternative animal model, Drosophila melanogaster, to investigate potential hazards of indoor air pollution. The inhalation toxicity of toluene and formaldehyde was investigated using comprehensive transcriptomics and computational behavior analyses. The ingenuity pathway analysis (IPA) based on microarray data suggests the involvement of pathways related to immune response, stress response, and metabolism in formaldehyde and toluene exposure based on hub molecules. We conducted a toxicity test using mutants of the representative genes in these pathways to explore the toxicological consequences of alterations of these pathways. Furthermore, extensive computational behavior analysis showed that exposure to either toluene or formaldehyde reduced most of the behavioral parameters of both wild-type and mutants. Interestingly, behavioral alteration caused by toluene or formaldehyde exposure was most severe in the p38b mutant, suggesting that the defects in the p38 pathway underlie behavioral alteration. Overall, the results indicate that exposure to toluene and formaldehyde via inhalation causes severe toxicity in Drosophila, by inducing significant alterations in gene expression and behavior, suggesting that Drosophila can be used as a potential alternative model in inhalation toxicity screening.

  2. Mechanisms of action of inhaled fibers, particles and nanoparticles in lung and cardiovascular diseases

    Directory of Open Access Journals (Sweden)

    Donaldson Kenneth

    2007-05-01

    Full Text Available Abstract Background A symposium on the mechanisms of action of inhaled airborne particulate matter (PM, pathogenic particles and fibers such as silica and asbestos, and nanomaterials, defined as synthetic particles or fibers less than 100 nm in diameter, was held on October 27 and 28, 2005, at the Environmental Protection Agency (EPA Conference Center in Research Triangle Park, North Carolina. The meeting was the eighth in a series of transatlantic conferences first held in Penarth, Wales, at the Medical Research Council Pneumoconiosis Unit (1979, that have fostered long-standing collaborations between researchers in the fields of mineralogy, cell and molecular biology, pathology, toxicology, and environmental/occupational health. Results The goal of this meeting, which was largely supported by a conference grant from the NHLBI, was to assemble a group of clinical and basic research scientists who presented and discussed new data on the mechanistic effects of inhaled particulates on the onset and development of morbidity and mortality in the lung and cardiovascular system. Another outcome of the meeting was the elucidation of a number of host susceptibility factors implicated in adverse health effects associated with inhaled pathogenic particulates. Conclusion New models and data presented supported the paradigm that both genetic and environmental (and occupational factors affect disease outcomes from inhaled particulates as well as cardiopulmonary responses. These future studies are encouraged to allow the design of appropriate strategies for prevention and treatment of particulate-associated morbidity and mortality, especially in susceptible populations.

  3. Development and evaluation of an inhalation chamber for in vivo tests

    Directory of Open Access Journals (Sweden)

    EDUARDO R. DA SILVA

    2017-08-01

    Full Text Available ABSTRACT The bioavailability, toxicity, and therapeutic efficacy of a drug is directly related to its administration route. The pulmonary route can be accessed by inhalation after fumigation, vaporization or nebulization. Thus, pharmacological and toxicological evaluation accessed by an apparatus specifically designed and validated for this type of administration is extremely important. Based on pre-existing models, an inhalation chamber was developed. This presents a central structure with five animal holders. The nebulized air passes directly and continuously through these holders and subsequently to an outlet. Evaluation of its operation was performed using clove essential oil, a nebulizer, and a flow meter. The air within the chamber was collected by static headspace and analyzed by gas chromatography with a flame ionization detector. For this purpose, a 2.5 minutes chromatographic method was developed. The air flow in each of the five outputs was 0.92 liters per minute. During the first minute, the chamber became saturated with the nebulized material. Homogeneous and continuous operation of the chamber was observed without accumulation of volatile material inside it for 25 minutes. The inhalation chamber works satisfactorily for in vivo tests with medicines designed to be administrated by inhalation.

  4. Safety and Toxicology of Cannabinoids.

    Science.gov (United States)

    Sachs, Jane; McGlade, Erin; Yurgelun-Todd, Deborah

    2015-10-01

    There is extensive research on the safety, toxicology, potency, and therapeutic potential of cannabis. However, uncertainty remains facilitating continued debate on medical and recreational cannabis policies at the state and federal levels. This review will include a brief description of cannabinoids and the endocannabinoid system; a summary of the acute and long-term effects of cannabis; and a discussion of the therapeutic potential of cannabis. The conclusions about safety and efficacy will then be compared with the current social and political climate to suggest future policy directions and general guidelines.

  5. Biological effects like cancer formation due to inhalational exposure to plutonium. What are evident in animal experiments?

    International Nuclear Information System (INIS)

    Oghiso, Yoichi

    2013-01-01

    Literatures on the title subject are reviewed and problems to be solved are given. There are 2 reports of dog experiments of inhaled Pu by Pacific Northwest Laboratory (PNL), which have given results incompatible/compatible with risk assessments hitherto: one with the micro-particle of Pu-nitrate, 239 Pu(NO 3 ) 4 , in which the dog lung is compared with human's by histology and autoradiography, presenting findings that differ from the previous ICRP assumption of the homogeneous distribution in the lung; and the other with 239 PuO 2 , indicating that non-tumorous diseases are agreeable with the determinative effect defined by ICRP. Other literatures have shown that effects of Pu inhalation differ dependently on the solubility of its chemical form and on its isotope ( 239 Pu and 238 Pu). Size of the inhaled Pu particle affects its deposition and thereby its influence on the air tract and other tissues. Rats are also used in Pu inhalation experiments. The significant increase of malignant lung tumor incidence is shown with 239 PuO 2 inhalation at >1 Gy lung absorbed dose by PNL and Inhalation Toxicology Research Institute (ITRI) and by National Institute of Radiological Sciences (NIRS), at >0.7 Gy and not at 239 PuO 2 inhalation in dogs involves the long-term decrease of peripheral lymphocytes, acute radiation pneumonia and chronic fibroid lung at 10-20 Gy, which can be a cause of death. There are many studies of the lung tumor formation at various carcinogenic steps in rats. Problems to be solved for the inhaled Pu compound are the elucidation of accuracy and validity concerning the metabolic parameters, alpha-ray dose assessment, dose rate effects of particle size; the biological factors modifying the metabolism and effect; and the relationship of cancer formation with non-tumorous diseases. (T.T)

  6. Passive inhalation of cannabis smoke

    Energy Technology Data Exchange (ETDEWEB)

    Law, B; Mason, P A; Moffat, A C; King, L J; Marks, V

    1984-09-01

    Six volunteers each smoked simultaneously, in a small unventilated room (volume 27 950 liter), a cannabis cigarette containing 17.1 mg delta 9-tetrahydrocannabinol (THC). A further four subjects - passive inhalers - remained in the room during smoking and afterwards for a total of 3 h. Blood and urine samples were taken from all ten subjects and analyzed by radioimmunoassay for THC metabolites. The blood samples from the passive subjects taken up to 3 h after the start of exposure to cannabis smoke showed a complete absence of cannabinoids. In contrast, their urine samples taken up to 6 h after exposure showed significant concentrations of cannabinoid metabolites (less than or equal to 6.8 ng ml-1). These data, taken with the results of other workers, show passive inhalation of cannabis smoke to be possible. These results have important implications for forensic toxicologists who are frequently called upon to interpret cannabinoid levels in body fluids.

  7. Inhaled plutonium oxide in dogs

    International Nuclear Information System (INIS)

    Park, J.F.

    1982-01-01

    This project is concerned with long-term experiments to determine the lifespan dose-effect relationships of inhaled 239 PuO 2 and 238 PuO 2 in beagles. Beagle dogs given a single exposure to 239 PuO 2 or 238 PuO 2 aerosols are being observed for lifespan dose-effect relationships. The 239 Pu body burden of the nine dogs that died of pulmonary-fibrosis-induced respiratory insufficiency during the first 3 yr after exposure was 1 to 12μCi. Nineteen of the dogs exposed to 238 Pu haved died during the first 7-1/2 yr after exposure due to bone and/or lung tumors; their body burdens at death ranged from 0.7 to 10μCi. Chronic lymphopenia was the earliest observed effect after inhalation of 239 PuO 2 or 238 PuO 2

  8. Systemic metabolic derangement, pulmonary effects, and insulin insufficiency following subchronic ozone exposure in rats

    International Nuclear Information System (INIS)

    Miller, Desinia B.; Snow, Samantha J.; Henriquez, Andres; Schladweiler, Mette C.; Ledbetter, Allen D.; Richards, Judy E.; Andrews, Debora L.; Kodavanti, Urmila P.

    2016-01-01

    Acute ozone exposure induces a classical stress response with elevated circulating stress hormones along with changes in glucose, protein and lipid metabolism in rats, with similar alterations in ozone-exposed humans. These stress-mediated changes over time have been linked to insulin resistance. We hypothesized that acute ozone-induced stress response and metabolic impairment would persist during subchronic episodic exposure and induce peripheral insulin resistance. Male Wistar Kyoto rats were exposed to air or 0.25 ppm or 1.00 ppm ozone, 5 h/day, 3 consecutive days/week (wk) for 13 wks. Pulmonary, metabolic, insulin signaling and stress endpoints were determined immediately after 13 wk or following a 1 wk recovery period (13 wk + 1 wk recovery). We show that episodic ozone exposure is associated with persistent pulmonary injury and inflammation, fasting hyperglycemia, glucose intolerance, as well as, elevated circulating adrenaline and cholesterol when measured at 13 wk, however, these responses were largely reversible following a 1 wk recovery. Moreover, the increases noted acutely after ozone exposure in non-esterified fatty acids and branched chain amino acid levels were not apparent following a subchronic exposure. Neither peripheral or tissue specific insulin resistance nor increased hepatic gluconeogenesis were present after subchronic ozone exposure. Instead, long-term ozone exposure lowered circulating insulin and severely impaired glucose-stimulated beta-cell insulin secretion. Thus, our findings in young-adult rats provide potential insights into epidemiological studies that show a positive association between ozone exposures and type 1 diabetes. Ozone-induced beta-cell dysfunction may secondarily contribute to other tissue-specific metabolic alterations following chronic exposure due to impaired regulation of glucose, lipid, and protein metabolism. - Highlights: • Subchronic episodic ozone exposure caused pulmonary and metabolic effects. • These

  9. Systemic metabolic derangement, pulmonary effects, and insulin insufficiency following subchronic ozone exposure in rats

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Desinia B. [Curriculum in Toxicology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina (United States); Snow, Samantha J. [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Henriquez, Andres [Curriculum in Toxicology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina (United States); Schladweiler, Mette C.; Ledbetter, Allen D.; Richards, Judy E.; Andrews, Debora L. [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Kodavanti, Urmila P., E-mail: kodavanti.urmila@epa.gov [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States)

    2016-09-01

    Acute ozone exposure induces a classical stress response with elevated circulating stress hormones along with changes in glucose, protein and lipid metabolism in rats, with similar alterations in ozone-exposed humans. These stress-mediated changes over time have been linked to insulin resistance. We hypothesized that acute ozone-induced stress response and metabolic impairment would persist during subchronic episodic exposure and induce peripheral insulin resistance. Male Wistar Kyoto rats were exposed to air or 0.25 ppm or 1.00 ppm ozone, 5 h/day, 3 consecutive days/week (wk) for 13 wks. Pulmonary, metabolic, insulin signaling and stress endpoints were determined immediately after 13 wk or following a 1 wk recovery period (13 wk + 1 wk recovery). We show that episodic ozone exposure is associated with persistent pulmonary injury and inflammation, fasting hyperglycemia, glucose intolerance, as well as, elevated circulating adrenaline and cholesterol when measured at 13 wk, however, these responses were largely reversible following a 1 wk recovery. Moreover, the increases noted acutely after ozone exposure in non-esterified fatty acids and branched chain amino acid levels were not apparent following a subchronic exposure. Neither peripheral or tissue specific insulin resistance nor increased hepatic gluconeogenesis were present after subchronic ozone exposure. Instead, long-term ozone exposure lowered circulating insulin and severely impaired glucose-stimulated beta-cell insulin secretion. Thus, our findings in young-adult rats provide potential insights into epidemiological studies that show a positive association between ozone exposures and type 1 diabetes. Ozone-induced beta-cell dysfunction may secondarily contribute to other tissue-specific metabolic alterations following chronic exposure due to impaired regulation of glucose, lipid, and protein metabolism. - Highlights: • Subchronic episodic ozone exposure caused pulmonary and metabolic effects. • These

  10. Two 238Pu inhalation incidents

    International Nuclear Information System (INIS)

    Fleming, R.R.; Hall, R.M.

    1978-06-01

    Two employees inhaled significant amounts of 238 Pu in separate unrelated contamination incidents in 1977. Both acute exposure incidents are described and the urine, feces, and in-vivo chest count data for each employee. Case B ( 238 PuNO 3 ) received 24 DTPA treatments beginning the day of the incident while, for medical reasons, Case A ( 238 PuO 2 ) received no therapy

  11. The Toxicology Education Summit: building the future of toxicology through education.

    Science.gov (United States)

    Barchowsky, Aaron; Buckley, Lorrene A; Carlson, Gary P; Fitsanakis, Vanessa A; Ford, Sue M; Genter, Mary Beth; Germolec, Dori R; Leavens, Teresa L; Lehman-McKeeman, Lois D; Safe, Stephen H; Sulentic, Courtney E W; Eidemiller, Betty J

    2012-06-01

    Toxicology and careers in toxicology, as well as many other scientific disciplines, are undergoing rapid and dramatic changes as new discoveries, technologies, and hazards advance at a blinding rate. There are new and ever increasing demands on toxicologists to keep pace with expanding global economies, highly fluid policy debates, and increasingly complex global threats to public health. These demands must be met with new paradigms for multidisciplinary, technologically complex, and collaborative approaches that require advanced and continuing education in toxicology and associated disciplines. This requires paradigm shifts in educational programs that support recruitment, development, and training of the modern toxicologist, as well as continued education and retraining of the midcareer professional to keep pace and sustain careers in industry, government, and academia. The Society of Toxicology convened the Toxicology Educational Summit to discuss the state of toxicology education and to strategically address educational needs and the sustained advancement of toxicology as a profession. The Summit focused on core issues of: building for the future of toxicology through educational programs; defining education and training needs; developing the "Total Toxicologist"; continued training and retraining toxicologists to sustain their careers; and, finally, supporting toxicology education and professional development. This report summarizes the outcomes of the Summit, presents examples of successful programs that advance toxicology education, and concludes with strategies that will insure the future of toxicology through advanced educational initiatives.

  12. Inhaled plutonium oxide in dogs

    International Nuclear Information System (INIS)

    Park, J.F.

    1985-01-01

    This project is concerned with long-term experiments to determine the lifespan dose-effect relationships of inhaled 239 PuO 2 and 238 PuO 2 in beagles. The data will be used to estimate the health effects of inhaled transuranics. Beagle dogs given a single exposure to 239 PuO 2 or 238 PuO 2 aerosols to obtain graded levels of initial lung burdens are being observed for lifespan dose-effect relationships. Mortality due to radiation pneumonitis and lung tumor increased in the four highest dose-level groups exposed to 239 PuO 2 , during the 13-yr postexposure period. During the 10 1/2 years after exposure to 238 PuO 2 , mortality due to lung and/or bone tumors increased in the three highest dose-level groups. Chronic lymphopenia, occurring 0.5 to 2 year after exposure, was the earliest observed effect after inhalation of either 239 PuO 2 or 238 PuO 2 in the four highest dose-level groups that had initial lung burdens greater than or equal to 80 nCi. 3 figures, 6 tables

  13. Cancer hazard from inhaled plutonium

    International Nuclear Information System (INIS)

    Gofman, J.W.

    1975-01-01

    The best estimate of the lung cancer potential in humans for inhaled insoluble compounds of plutonium (such as PuO 2 particles) has been grossly underestimated by such authoritative bodies as the International Commission on Radiological Protection and the British Medical Research Council. Calculations are presented of lung cancer induction by 239 Pu as insoluble particles and for deposited reactor-grade Pu. The reason for the gross underestimate of the carcinogenic effects of Pu by ICRP or the British Medical Research Council (BMRC) is their use of a totally unrealistic idealized model for the clearance of deposited Pu from the lungs and bronchi plus their non-recognition of the bronchi as the true site for most human lung cancers. The erroneous model used by such organizations also fails totally to take into account the effect of cigarette-smoking upon the physiological function of human lungs. Plutonium nuclides, such as 239 Pu, or other alpha particle-emitting nuclides, in an insoluble form represent an inhalation cancer hazard in a class some 100,000 times more potent than the potent chemical carcinogens, weight for weight. The already-existing lung cancer data for beagle dogs inhaling insoluble PuO 2 particles is clearly in order of magnitude agreement with calculations for humans

  14. The Emergence of Systematic Review in Toxicology.

    Science.gov (United States)

    Stephens, Martin L; Betts, Kellyn; Beck, Nancy B; Cogliano, Vincent; Dickersin, Kay; Fitzpatrick, Suzanne; Freeman, James; Gray, George; Hartung, Thomas; McPartland, Jennifer; Rooney, Andrew A; Scherer, Roberta W; Verloo, Didier; Hoffmann, Sebastian

    2016-07-01

    The Evidence-based Toxicology Collaboration hosted a workshop on "The Emergence of Systematic Review and Related Evidence-based Approaches in Toxicology," on November 21, 2014 in Baltimore, Maryland. The workshop featured speakers from agencies and organizations applying systematic review approaches to questions in toxicology, speakers with experience in conducting systematic reviews in medicine and healthcare, and stakeholders in industry, government, academia, and non-governmental organizations. Based on the workshop presentations and discussion, here we address the state of systematic review methods in toxicology, historical antecedents in both medicine and toxicology, challenges to the translation of systematic review from medicine to toxicology, and thoughts on the way forward. We conclude with a recommendation that as various agencies and organizations adapt systematic review methods, they continue to work together to ensure that there is a harmonized process for how the basic elements of systematic review methods are applied in toxicology. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology.

  15. 42 CFR 493.845 - Standard; Toxicology.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Standard; Toxicology. 493.845 Section 493.845 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.845 Standard; Toxicology. (a) Failure to attain a score of at least 80 percent of...

  16. Blood transcriptomics: applications in toxicology

    Science.gov (United States)

    Joseph, Pius; Umbright, Christina; Sellamuthu, Rajendran

    2015-01-01

    The number of new chemicals that are being synthesized each year has been steadily increasing. While chemicals are of immense benefit to mankind, many of them have a significant negative impact, primarily owing to their inherent chemistry and toxicity, on the environment as well as human health. In addition to chemical exposures, human exposures to numerous non-chemical toxic agents take place in the environment and workplace. Given that human exposure to toxic agents is often unavoidable and many of these agents are found to have detrimental human health effects, it is important to develop strategies to prevent the adverse health effects associated with toxic exposures. Early detection of adverse health effects as well as a clear understanding of the mechanisms, especially at the molecular level, underlying these effects are key elements in preventing the adverse health effects associated with human exposure to toxic agents. Recent developments in genomics, especially transcriptomics, have prompted investigations into this important area of toxicology. Previous studies conducted in our laboratory and elsewhere have demonstrated the potential application of blood gene expression profiling as a sensitive, mechanistically relevant and practical surrogate approach for the early detection of adverse health effects associated with exposure to toxic agents. The advantages of blood gene expression profiling as a surrogate approach to detect early target organ toxicity and the molecular mechanisms underlying the toxicity are illustrated and discussed using recent studies on hepatotoxicity and pulmonary toxicity. Furthermore, the important challenges this emerging field in toxicology faces are presented in this review article. PMID:23456664

  17. Evolution of toxicology information systems

    Energy Technology Data Exchange (ETDEWEB)

    Wassom, J.S.; Lu, P.Y. [Oak Ridge National Laboratory, TN (United States)

    1990-12-31

    Society today is faced with new health risk situations that have been brought about by recent scientific and technical advances. Federal and state governments are required to assess the many potential health risks to exposed populations from the products (chemicals) and by-products (pollutants) of these advances. Because a sound analysis of any potential health risk should be based on the use of relevant information, it behooves those individuals responsible for making the risk assessments to know where to obtain needed information. This paper reviews the origins of toxicology information systems and explores the specialized information center concept that was proposed in 1963 as a means of providing ready access to scientific and technical information. As a means of illustrating this concept, the operation of one specialized information center (the Environmental Mutagen Information Center at Oak Ridge National Laboratory) will be discussed. Insights into how toxicological information resources came into being, their design and makeup, will be of value to those seeking to acquire information for risk assessment purposes. 7 refs., 1 fig., 4 tabs.

  18. Toxicological profile for thorium. Draft report (Final)

    International Nuclear Information System (INIS)

    1990-10-01

    The ATSDR Toxicological Profile for Thorium is intended to characterize succinctly the toxicological and health effects information for the substance. It identifies and reviews the key literature that describes the substance's toxicological properties. Other literature is presented but described in less detail. The profile is not intended to be an exhaustive document; however, more comprehensive sources of specialty information are referenced. The profile begins with a public health statement, which describes in nontechnical language the substance's relevant toxicological properties. Following the statement is material that presents levels of significant human exposure and, where known, significant health effects. The adequacy of information to determine the substance's health effects is described. Research gaps in nontoxic and health effects information are described. Research gaps that are of significance to the protection of public health will be identified in a separate effort. The focus of the document is on health and toxicological information

  19. Toxicological profile for uranium. Final report

    International Nuclear Information System (INIS)

    1990-12-01

    The ATSDR Toxicological Profile for Uranium is intended to characterize succinctly the toxicological and health effects information for the substance. It identifies and reviews the key literature that describes the substances's toxicological properties. Other literature is presented but described in less detail. The profile is not intended to be an exhaustive document; however, more comprehensive sources of specialty information are referenced. The profile begins with a public health statement, which describes in nontechnical language the substance's relevant toxicological properties. Following the statement is material that presents levels of significant human exposure and, where known, significant health effects. The adequacy of information to determine the substance's health effects is described. Research gaps in nontoxic and health effects information are described. Research gaps that are of significance to the protection of public health will be identified in a separate effort. The focus of the document is on health and toxicological information

  20. Toxicological profile for radon. Final report

    International Nuclear Information System (INIS)

    1990-12-01

    The ATSDR Toxicological Profile for Radon is intended to characterize succinctly the toxicological and health effects information for the substance. It identifies and reviews the key literature that describes the substance's toxicological properties. Other literature is presented but described in less detail. The profile is not intended to be an exhaustive document; however, more comprehensive sources of specialty information are referenced. The profile begins with a public health statement, which describes in nontechnical language the substance's relevant toxicological properties. Following the statement is material that presents levels of significant human exposure and, where known, significant health effects. The adequacy of information to determine the substance's health effects is described. Research gaps in nontoxic and health effects information are described. Research gaps that are of significance to the protection of public health will be identified in a separate effort. The focus of the document is on health and toxicological information

  1. Toxicological profile for plutonium. Final report

    International Nuclear Information System (INIS)

    1990-12-01

    The ATSDR Toxicological Profile for Plutonium is intended to characterize succinctly the toxicological and health effects information for the substance. It identifies and reviews the key literature that describes the substance's toxicological properties. Other literature is presented but described in less detail. The profile is not intended to be an exhaustive document; however, more comprehensive sources of specialty information are referenced. The profile begins with a public health statement, which describes in nontechnical language the substance's relevant toxicological properties. Following the statement is material that presents levels of significant human exposure and, where known, significant health effects. The adequacy of information to determine the substance's health effects is described. Research gaps in nontoxic and health effects information are described. Research gaps that are of significance to the protection of public health will be identified in a separate effort. The focus of the document is on health and toxicological information

  2. Toxicological profile for radium. Final report

    International Nuclear Information System (INIS)

    1990-12-01

    The ATSDR Toxicological Profile for Radium is intended to characterize succinctly the toxicological and health effects information for the substance. It identifies and reviews the key literature that describes the substances' toxicological properties. Other literature is presented but described in less detail. The profile is not intended to be an exhaustive document; however, more comprehensive sources of specialty information are referenced. The profile begins with a public health statement, which describes in nontechnical language the substance's relevant toxicological properties. Following the statement is material that presents levels of significant human exposure and, where known, significant health effects. The adequacy of information to determine the substance's health effects is described. Research gaps in nontoxic and health effects information are described. Research gaps that are of significance to the protection of public health will be identified in a separate effort. The focus of the document is on health and toxicological information

  3. Toxicology

    Science.gov (United States)

    Macewen, J. W.

    1973-01-01

    Oxygen toxicity is examined, including the effects of oxygen partial pressure variations on toxicity and oxygen effects on ozone and nitrogen dioxide toxicity. Toxicity of fuels and oxidizers, such as hydrazines, are reported. Carbon monoxide, spacecraft threshold limit values, emergency exposure limits, spacecraft contaminants, and water quality standards for space missions are briefly summarized.

  4. Space Toxicology: Environmental Health Considerations during Spaceflight Operations and Potential Paths for Research

    Science.gov (United States)

    Khan-Mayberry, Noreen N.; Sundaresan, Alemalu

    2009-01-01

    Space Toxicology is a specialized discipline for spaceflight, space habitation and occupation of celestial bodies including planets, moons and asteroids [1]. Astronaut explorers face unique challenges to their health while working and living with limited resources for rescue and medical care during space operation. At its core the practice of space toxicology to identify, assess and predict potential chemical contaminants and limit the astronaut s exposure to these environmental factors in order to protect crew health. Space toxicologists are also charged with setting safe exposure limits that will protect the astronaut against a multitude of chemical exposures, in a physiologically altered state. In order to maintain sustained occupation in space, toxicological risks are gauged and managed within the context of isolation, continual exposures, reuse of air and water, limited rescue options, and the necessary use of highly toxic compounds required for propulsion. As the space program move towards human presence and exploration other celestial bodies in situ toxicological risks, such as inhalation of unusual and/or reactive mineral dusts must also be analyzed and controlled. Placing humans for long-term presence in space creates several problems and challenges to the long-term health of the crew, such as bone-loss and immunological challenges and has spurred research into acute, chronic and episodic exposure of the pulmonary system to mineral dusts [2]. NASA has demonstrated that lunar soil contains several types of reactive dusts, including an extremely fine respirable component. In order to protect astronaut health, NASA is now investigating the toxicity of this unique class of dusts. Understanding how these reactive components behave "biochemically" in a moisture-rich pulmonary environment will aid in determining how toxic these particles are to humans. The data obtained from toxicological examination of lunar dusts will determine the human risk criteria for lunar

  5. A comprehensive evaluation of the toxicology of experimental cigarettes manufactured with banded papers.

    Science.gov (United States)

    Werley, Michael S; Jerome, Ann M; DeSoi, Darren J; Coggins, Christopher R E; Oldham, Michael J; McKinney, Willie J

    2013-01-01

    To comply with state requirements, cigarette manufacturers have added low-permeability bands to the cigarette paper. These bands can extinguish the cigarette when it is no longer being puffed by a smoker. This study was conducted to evaluate the toxicology resulting from the addition of different types of bands to experimental cigarettes. A battery of assays that are typically used in toxicology studies with cigarette smoke, namely smoke chemistry, in vitro mutagenicity and cytotoxicity, and inhalation studies with rats, were used to evaluate different band characteristics added to cigarette paper. Although differences in the amount of band material was associated with an increase in some metals measured in mainstream tobacco smoke, it was not dose responsive to any band design parameter (base paper permeability, band width, band spacing, band chalk amount, or citrate). Occasional, minor differences were produced by the different types of bands; overall, there was no increased toxicity. Although there were increases and decreases in some mainstream smoke constituents, the in vitro and in vivo testing performed demonstrated that low-permeability bands on cigarettes do not modify the toxicity of smoke inhaled by smokers.

  6. Titanium dioxide nanoparticles: a review of current toxicological data

    Science.gov (United States)

    2013-01-01

    Titanium dioxide (TiO2) nanoparticles (NPs) are manufactured worldwide in large quantities for use in a wide range of applications. TiO2 NPs possess different physicochemical properties compared to their fine particle (FP) analogs, which might alter their bioactivity. Most of the literature cited here has focused on the respiratory system, showing the importance of inhalation as the primary route for TiO2 NP exposure in the workplace. TiO2 NPs may translocate to systemic organs from the lung and gastrointestinal tract (GIT) although the rate of translocation appears low. There have also been studies focusing on other potential routes of human exposure. Oral exposure mainly occurs through food products containing TiO2 NP-additives. Most dermal exposure studies, whether in vivo or in vitro, report that TiO2 NPs do not penetrate the stratum corneum (SC). In the field of nanomedicine, intravenous injection can deliver TiO2 nanoparticulate carriers directly into the human body. Upon intravenous exposure, TiO2 NPs can induce pathological lesions of the liver, spleen, kidneys, and brain. We have also shown here that most of these effects may be due to the use of very high doses of TiO2 NPs. There is also an enormous lack of epidemiological data regarding TiO2 NPs in spite of its increased production and use. However, long-term inhalation studies in rats have reported lung tumors. This review summarizes the current knowledge on the toxicology of TiO2 NPs and points out areas where further information is needed. PMID:23587290

  7. Titanium dioxide nanoparticles: a review of current toxicological data.

    Science.gov (United States)

    Shi, Hongbo; Magaye, Ruth; Castranova, Vincent; Zhao, Jinshun

    2013-04-15

    Titanium dioxide (TiO2) nanoparticles (NPs) are manufactured worldwide in large quantities for use in a wide range of applications. TiO2 NPs possess different physicochemical properties compared to their fine particle (FP) analogs, which might alter their bioactivity. Most of the literature cited here has focused on the respiratory system, showing the importance of inhalation as the primary route for TiO2 NP exposure in the workplace. TiO2 NPs may translocate to systemic organs from the lung and gastrointestinal tract (GIT) although the rate of translocation appears low. There have also been studies focusing on other potential routes of human exposure. Oral exposure mainly occurs through food products containing TiO2 NP-additives. Most dermal exposure studies, whether in vivo or in vitro, report that TiO2 NPs do not penetrate the stratum corneum (SC). In the field of nanomedicine, intravenous injection can deliver TiO2 nanoparticulate carriers directly into the human body. Upon intravenous exposure, TiO2 NPs can induce pathological lesions of the liver, spleen, kidneys, and brain. We have also shown here that most of these effects may be due to the use of very high doses of TiO2 NPs. There is also an enormous lack of epidemiological data regarding TiO2 NPs in spite of its increased production and use. However, long-term inhalation studies in rats have reported lung tumors. This review summarizes the current knowledge on the toxicology of TiO2 NPs and points out areas where further information is needed.

  8. How to use an inhaler - no spacer

    Science.gov (United States)

    ... MDI) administration - no spacer; Bronchial nebulizer; Wheezing - nebulizer; Reactive airway - nebulizer; COPD - ... 66. National Asthma Education and Prevention Program website. How to use a metered-dose inhaler. ...

  9. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... on Spirometry Parents Preventing and Controlling Tools for Control Triggers Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers Data, Statistics, ...

  10. Inhalation developmental toxicology studies: Teratology study of methyl ethyl ketone in mice: Final report

    International Nuclear Information System (INIS)

    Mast, T.J.; Dill, J.A.; Evanoff, J.J.; Rommereim, R.L.; Weigel, R.J.; Westerberg, R.B.

    1989-02-01

    Methyl ethyl ketone (MEK) is a widely used industrial solvent which results in considerable human exposure. In order to assess the potential for MEK to cause developmental toxicity in rodents, four groups of Swiss (CD-1) mice were exposed to 0, 400, 1000 or 3000 ppM MEK vapors, 7 h/day, 7 dy/wk. Ten virgin females and ∼30 plug-positive females per group were exposed concurrently for 10 consecutive days (6--15 dg for mated mice). Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice on 18 dg. Uterine implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. Exposure of pregnant mice to these concentrations of MEK did not result in apparent maternal toxicity, although there was a slight, treatment-correlated increase in liver to body weight ratios which was significant for the 3000-ppM group. Mild developmental toxicity was evident at 3000-ppM as a reduction in mean fetal body weight. This reduction was statistically significant for the males only, although the relative decrease in mean fetal body weight was the same for both sexes. 17 refs., 4 figs., 10 tabs

  11. Inhalation developmental toxicology studies: Teratology study of isoprene in mice and rats: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Mast, T.J.; Evanoff, J.J.; Stoney, K.H.; Westerberg, R.B.; Rommereim, R.L.; Weigel, R.J.

    1989-01-01

    Isoprene, a reactive, branched diene, is used in large quantities in the manufacture of polyisoprene and as a copolymer in the synthesis of butyl rubber. The potential for isoprene to cause developmental toxicity was assessed in rodents, by exposing four groups each of Sprague-Dawley rats and Swiss (CD-1) mice to 0, 280, 1400, or 7000 ppM isoprene vapors, 6 h/day, 7 day/wk. Each treatment group consisted of 10 virgin females (for comparison), and approx.30 positively mated rats or mice. Positively mated mice were exposed on days 6-17 of gestation (dg), and rats on 6-19 dg. The day of plug or sperm detection was designated as 0 dg. Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice (rats, 20 dg; mice, 18 dg). Implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. 31 refs., 6 figs., 19 tabs.

  12. Inhalation developmental toxicology studies: Developmental toxicity of chloroprene vapors in New Zealand white rabbits. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Mast, T.J.; Evanoff, J.J.; Westerberg, R.B.; Rommereim, R.L.; Weigel, R.J.

    1994-04-01

    Chloroprene, 2-chloro-1,3-butadiene, is a colorless liquid with a pungent ethereal odor that is primarily used as an intermediate in the manufacture of neoprene rubber, and has been used as such since about 1930. This study addressed the potential for chloroprene to cause developmental toxicity in New Zealand white rabbits following gestational exposure to 0, 10, 40, or 175 ppm chloroprene vapors, 6h/dy, 7dy/wk. Each treatment group consisted of 15 artificially inseminated females exposed on 6 through 28 days of gestation (dg). Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice on 29 dg. Implants were enumerated and their status recorded and live fetuses were examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. There were no overt signs of maternal toxicity and the change in maternal body weight over the course of the study was not affected. Exposure of pregnant rabbits to chloroprene vapors on 6-28 dg had no effect on the number of implantation, the mean percent of live pups per litter, or on the incidence of resorptions per litter. The incidence of fetal malformations was not increased by exposure to chloroprene. Results of this study indicate that gestational exposure of New Zealand white rabbits to 10, 40, or 175 ppm chloroprene did not result in observable toxicity to either the dam or the offspring.

  13. Inhalation developmental toxicology studies: Teratology study of n-hexane in mice: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Mast, T.J.; Decker, J.R.; Stoney, K.H.; Westerberg, R.B.; Evanoff, J.J.; Rommereim, R.L.; Weigel, R.J.

    1988-05-01

    Gestational exposure to n-hexane resulted in an increase in the number of resorbed fetuses for exposure groups relative to the control group; however, the increases were not directly correlated to exposure concentration. The differences were statistically significant for the 200-ppM with respect to total intrauterine death (early plus late resorptions), and with respect to late resorptions for the 5000-ppM group. A small, but statistically significant, reduction in female (but not male) fetal body weight relative to the control group was observed at the 5000-ppM exposure level. There were no exposure-related increases in any individual fetal malformation or variation, nor was there any increase in the incidence of combined malformations or variations. Gestational exposure of CD-1 mice to n-hexane vapors appeared to cause a degree of concentration-related developmental toxicity in the absence of overt maternal toxicity, but the test material was not found to be teratogenic. This developmental toxicity was manifested as an increase in the number of resorptions per litter for all exposure levels, and as a decrease in the uterine: extra-gestational weight gain ratio at the 5000-ppM exposure level. Because of the significant increase in the number of resorptions at the 200-ppM exposure level, a no observable effect level (NOEL) for developmental toxicity was not established for exposure of mice to 200, 1000 or 5000-ppM n-hexane vapors. 21 refs., 3 figs., 9 tabs.

  14. Inhalation developmental toxicology studies: Teratology study of methyl ethyl ketone in mice: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Mast, T.J.; Dill, J.A.; Evanoff, J.J.; Rommereim, R.L.; Weigel, R.J.; Westerberg, R.B.

    1989-02-01

    Methyl ethyl ketone (MEK) is a widely used industrial solvent which results in considerable human exposure. In order to assess the potential for MEK to cause developmental toxicity in rodents, four groups of Swiss (CD-1) mice were exposed to 0, 400, 1000 or 3000 ppM MEK vapors, 7 h/day, 7 dy/wk. Ten virgin females and approx.30 plug-positive females per group were exposed concurrently for 10 consecutive days (6--15 dg for mated mice). Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice on 18 dg. Uterine implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. Exposure of pregnant mice to these concentrations of MEK did not result in apparent maternal toxicity, although there was a slight, treatment-correlated increase in liver to body weight ratios which was significant for the 3000-ppM group. Mild developmental toxicity was evident at 3000-ppM as a reduction in mean fetal body weight. This reduction was statistically significant for the males only, although the relative decrease in mean fetal body weight was the same for both sexes. 17 refs., 4 figs., 10 tabs.

  15. Inhalation developmental toxicology studies: Teratology study of acetone in mice and rats: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Mast, T.J.; Evanoff, J.J.; Rommereim, R.L.; Stoney, K.H.; Weigel, R.J.; Westerberg, R.B.

    1988-11-01

    Acetone, an aliphatic ketone, is a ubiquitous industrial solvent and chemical intermediate; consequently, the opportunity for human exposure is high. The potential for acetone to cause developmental toxicity was assessed in Sprague-Dawley rats exposed to 0, 440, 2200, or 11000 ppm, and in Swiss (CD-1) mice exposed to 0, 440, 2200, and 6600 ppm acetone vapors, 6 h/day, 7 days/week. Each of the four treatment groups consisted of 10 virgin females (for comparison), and approx.32 positively mated rats or mice. Positively mated mice were exposed on days 6-17 of gestation (dg), and rats on 6-19 dg. The day of plug or sperm detection was designated as 0 dg. Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice (rats, 20 dg; mice, 18 dg). Implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. 46 refs., 6 figs., 27 tabs.

  16. Subchronic (26- and 52-week) toxicity and irritation studies of a novel microbicidal gel formulation containing sodium lauryl sulfate in animal models.

    Science.gov (United States)

    Piret, Jocelyne; Laforest, Geneviève; Bussières, Martin; Bergeron, Michel G

    2008-03-01

    The safety of an ethylene oxide/propylene oxide gel formulation containing sodium lauryl sulfate (2%, w/w), that could be a potent candidate as a topical microbicide, has been evaluated. More specifically, the subchronic (26- and 52-week) toxicity of the formulation when applied intravaginally as well as its irritating potential for the rectal, penile, eye, skin and buccal mucosa have been examined in animal models. The results showed that the vaginal administration of the gel formulation containing sodium lauryl sulfate once and twice daily (with doses 12 +/- 2 h apart) for 26 weeks to rats and for 52 weeks to rabbits induced slight to moderate histopathological alterations. When the formulation was applied intrarectally to male and female rabbits once and twice daily (with doses 12 +/- 2 h apart) for 14 days, no macroscopic or microscopic changes were reported. For both vaginal and rectal dosing, no effect was seen on the haematology, coagulation and serum chemistry parameters as well as on the body weight of animals and the relative organ weights. Other sporadic macroscopic and histopathological findings were incidental in origin and of no toxicological significance. The gel formulation containing sodium lauryl sulfate was considered as mildly irritating for the penile mucosa of rabbits, non-irritating for the eye of rabbits, mildly irritating for the skin in a rabbit model and non-irritating for the hamster cheek pouch. It is suggested that the gel formulation containing sodium lauryl sulfate is safe for most tissues that could be exposed to the product under normal use.

  17. Method Development in Forensic Toxicology.

    Science.gov (United States)

    Peters, Frank T; Wissenbach, Dirk K; Busardo, Francesco Paolo; Marchei, Emilia; Pichini, Simona

    2017-01-01

    In the field of forensic toxicology, the quality of analytical methods is of great importance to ensure the reliability of results and to avoid unjustified legal consequences. A key to high quality analytical methods is a thorough method development. The presented article will provide an overview on the process of developing methods for forensic applications. This includes the definition of the method's purpose (e.g. qualitative vs quantitative) and the analytes to be included, choosing an appropriate sample matrix, setting up separation and detection systems as well as establishing a versatile sample preparation. Method development is concluded by an optimization process after which the new method is subject to method validation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Testing of Binders Toxicological Effects

    Science.gov (United States)

    Strokova, V.; Nelyubova, V.; Rykunova, M.

    2017-11-01

    The article presents the results of a study of the toxicological effect of binders with different compositions on the vital activity of plant and animal test-objects. The analysis of the effect on plant cultures was made on the basis of the phytotesting data. The study of the effect of binders on objects of animal origin was carried out using the method of short-term testing. Based on the data obtained, binders are ranked according to the degree of increase in the toxic effect: Gypsum → Portland cement → Slag Portland cement. Regardless of the test-object type, the influence of binders is due to the release of various elements (calcium ions or heavy metals) into the solution. In case of plant cultures, the saturation of the solution with elements has a positive effect (there is no inhibitory effect), and in case of animal specimens - an increase in the toxic effect.

  19. Information resources in toxicology--Italy

    International Nuclear Information System (INIS)

    Preziosi, Paolo; Dracos, Adriana; Marcello, Ida

    2003-01-01

    The purpose of the present paper is to provide an overview of current resources in the field of toxicology in Italy. The discussion will begin with a brief history of toxicology in this country, which includes the study of the toxicity of plants and other natural substances, and the birth of industrial and forensic toxicology. We will also provide information on research, education, and hazard control in the field of toxicology. Within this context we will examine the public bodies responsible for surveillance and regulatory activities, state-owned and private structures involved in toxicological research, and the educational programs and research activities of universities. Particular emphasis will be placed on the activities of the National Health Service, which plays an important role in areas such as clinical toxicology, food safety, and animal health, as well as those of national and regional agencies dedicated to the protection of the environment. The presentation will be organized as follows: - A Brief History of Toxicology in Italy; - Professional Societies; - National Health Service; - National Bodies; - Resources for the Environment; - Biomedical Websites; - Recent Publications; - Research Structures; - Graduate and Postgraduate Programs; - Legislation

  20. Predictive toxicology: the paths of the future

    International Nuclear Information System (INIS)

    Detilleux, Ph.; Vallier, L.; Legallais, C.; Leclerc, E.; Prot, J.M.; Choucha, L.; Baudoin, R.; Dufresne, M.; Gautier, A.; Carpentier, B.; Mansuy, D.; Pery, A.; Brochot, C.; Manivet, Ph.; Rabilloud, Th.; Spire, C.; Coumoul, X.; Junot, Ch.; Laprevote, O.; Le pape, A.; Le Guevel, R.; Tourneur, E.; Ben Mkaddem, S.; Chassin, C.; Aloulou, M.; Goujon, J.M.; Hertif, A.; Ouali, N.; Vimont, S.; Monteiro, R.; Rondeau, E.; Elbim, C.; Werts, C.; Vandewalle, A.; Ben Mkaddem, S.; Pedruzzi, E.; Coant, N.; Bens, M.; Cluzeaud, F.; Ogier-Denis, E.; Pongnimitprasert, N.; Babin-Chevaye, C.; Fay, M.; Bernard, M.; Dupuy, C.; Ei Benna, J.; Gougerot-Pocidale, M.A.; Braut-Boucher, F.; Pinton, Ph.; Lucioli, J.; Tsybulskyy, D.; Joly, B.; Laffitte, J.; Bourges-Abella, N.; Oswald, I.P.; Kolf-Clauw, M.; Pierre, St.; Bats, A.S.; Chevallier, A.; Bui, L.Ch.; Ambolet-Camoit, A.; Garlatti, M.; Aggerbeck, M.; Barouki, R.; Al Khansa, I.; Blanck, O.; Guillouzo, A.; Bars, R.; Rouas, C.; Bensoussan, H.; Suhard, D.; Tessier, C.; Grandcolas, L.; Pallardy, M.; Gueguen, Y.; Sparfel, L.; Pinel-Marie, M.L.; Boize, M.; Koscielny, S.; Desmots, S.; Pery, A.; Fardel, O.; Alvergnas, M.; Rouleau, A.; Lucchi, G.; Mantion, G.; Heyd, B.; Richert, L.; Ducoroy, P.; Martin, H.; Val, St.; Martinon, L.; Cachier, H.; Yahyaoui, A.; Marfaing, H.; Baeza-Squiban, A.; Martin-Chouly, C.; Bonvallet, M.; Morzadec, C.; Fardel, O.; Vernhet, L.; Baverel, G.; El Hage, M.; Nazaret, R.; Conjard-Duplany, A.; Ferrier, B.; Martin, G.; Legendre, A.; Desmots, S.; Lecomte, A.; Froment, P.; Habert, R.; Lemazurier, E.; Robinel, F.; Dupont, O.; Sanfins, E.; Dairou, J.; Chaffotte, A.F.; Busi, F.; Rodrigues Lima, F.; Dupret, J.M.; Mayati, A.; Le Ferrec, E.; Levoin, N.; Paris, H.; Uriac, Ph.; N'Diaye, M.; Lagadic-Gossmann, D.; Fardel, O.; Assemat, E.; Boublil, L.; Borot, M.C.; Marano, F.; Baeza-Squiban, A.; Martiny, V.Y.; Moroy, G.; Badel, A.; Miteva, M.A.; Hussain, S.; Ferecatu, I.; Borot, C.; Andreau, K.; Baeza-Squiban, A.; Marano, F.; Boland, S.; Leroux, M.; Zucchini-Pascal, N.; Peyre, L.; Rahmani, R.; Buron, N.; Porcedou, M.; Fromenty, B.; Borgne-Sanchez, A.; Rogue, A.; Spire, C.; Claude, N.; Guillouzo, A.

    2010-01-01

    Prevention of possible noxious effects in relation with the exposure to one or several chemical, physical or biological agents present in our domestic or professional environment is one of today's big public health stakes. Another stake is the better assessment of the risks linked with the use of health-care products. The efficacy and predictiveness of toxicology studies are directly related to the combination of alternate complementary methods and animal experiments (obtaining data from different species and with different models: in vitro, ex vivo and in vivo). Despite important efforts, the toxicological evaluation remains perfectible. The proceedings of this 2010 congress of the French Society of cell pharmaco-toxicology deal with recent advances, both scientific and technological, in 'predictive toxicology'. Four main topics are approached: cell and organ models, 'omics', in silico modeling, and new technologies (imaging, cell ships, high-speed processing). Among the different presentations, 3 abstracts present some recent advances in imaging techniques applied to toxicology studies. These are: 1 - first uses in toxicology of TOF-SIMS mass spectroscopy imaging (O. Laprevote, Paris-Descartes Univ. (FR)); 2 - Small animal imaging, a tool for predictive toxicology (A. Le Pape, CNRS Orleans (FR)); 3 - uranium localization at cell level using SIMS imaging technique (C. Rouas et al., IRSN Fontenay-aux-Roses (FR)). (J.S.)

  1. A primer on systematic reviews in toxicology.

    Science.gov (United States)

    Hoffmann, Sebastian; de Vries, Rob B M; Stephens, Martin L; Beck, Nancy B; Dirven, Hubert A A M; Fowle, John R; Goodman, Julie E; Hartung, Thomas; Kimber, Ian; Lalu, Manoj M; Thayer, Kristina; Whaley, Paul; Wikoff, Daniele; Tsaioun, Katya

    2017-07-01

    Systematic reviews, pioneered in the clinical field, provide a transparent, methodologically rigorous and reproducible means of summarizing the available evidence on a precisely framed research question. Having matured to a well-established approach in many research fields, systematic reviews are receiving increasing attention as a potential tool for answering toxicological questions. In the larger framework of evidence-based toxicology, the advantages and obstacles of, as well as the approaches for, adapting and adopting systematic reviews to toxicology are still being explored. To provide the toxicology community with a starting point for conducting or understanding systematic reviews, we herein summarized available guidance documents from various fields of application. We have elaborated on the systematic review process by breaking it down into ten steps, starting with planning the project, framing the question, and writing and publishing the protocol, and concluding with interpretation and reporting. In addition, we have identified the specific methodological challenges of toxicological questions and have summarized how these can be addressed. Ultimately, this primer is intended to stimulate scientific discussions of the identified issues to fuel the development of toxicology-specific methodology and to encourage the application of systematic review methodology to toxicological issues.

  2. 40 CFR 798.2450 - Inhalation toxicity.

    Science.gov (United States)

    2010-07-01

    ... York: Macmillan Publishing Co. Inc. 1975). (3) MacFarland, H.N. “Respiratory Toxicology,” Essays in Toxicology. Ed. W.J. Hayes. Vol. 7 (New York: Academic Press, 1976) pp. 121-154. (4) National Academy of...

  3. Historical perspectives on cadmium toxicology

    International Nuclear Information System (INIS)

    Nordberg, Gunnar F.

    2009-01-01

    The first health effects of cadmium (Cd) were reported already in 1858. Respiratory and gastrointestinal symptoms occurred among persons using Cd-containing polishing agent. The first experimental toxicological studies are from 1919. Bone effects and proteinuria in humans were reported in the 1940's. After World War II, a bone disease with fractures and severe pain, the itai-itai disease, a form of Cd-induced renal osteomalacia, was identified in Japan. Subsequently, the toxicokinetics and toxicodynamics of Cd were described including its binding to the protein metallothionein. International warnings of health risks from Cd-pollution were issued in the 1970's. Reproductive and carcinogenic effects were studied at an early stage, but a quantitative assessment of these effects in humans is still subject to considerable uncertainty. The World Health Organization in its International Program on Chemical Safety, WHO/IPCS (1992) (Cadmium. Environmental Health Criteria Document 134, IPCS. WHO, Geneva, 1-280.) identified renal dysfunction as the critical effect and a crude quantitative evaluation was presented. In the 1990's and 2000 several epidemiological studies have reported adverse health effects, sometimes at low environmental exposures to Cd, in population groups in Japan, China, Europe and USA (reviewed in other contributions to the present volume). The early identification of an important role of metallothionein in cadmium toxicology formed the basis for recent studies using biomarkers of susceptibility to development of Cd-related renal dysfunction such as gene expression of metallothionein in peripheral lymphocytes and autoantibodies against metallothionein in blood plasma. Findings in these studies indicate that very low exposure levels to cadmium may give rise to renal dysfunction among sensitive subgroups of human populations such as persons with diabetes.

  4. Inhaled ciclesonide versus inhaled budesonide or inhaled beclomethasone or inhaled fluticasone for chronic asthma in adults: a systematic review

    Directory of Open Access Journals (Sweden)

    Halpin David MG

    2006-06-01

    Full Text Available Abstract Background Ciclesonide is a new inhaled corticosteroids licensed for the prophylactic treatment of persistent asthma in adults. Currently beclomethasone dipropionate, budesonide and fluticasone propionate are the most commonly prescribed inhaled corticosteroids for the treatment of asthma but there has been no systematic review comparing the effectiveness and safety ciclesonide to these agents. We therefore aimed to systematically review published randomised controlled trials of the effectiveness and safety of ciclesonide compared to alternative inhaled corticosteroids in people with asthma. Methods We performed literature searches on MEDLINE, EMBASE, PUBMED, the COCHRANE LIBRARY and various Internet evidence sources for randomised controlled trials or systematic reviews comparing ciclesonide to beclomethasone or budesonide or fluticasone in adult humans with persistent asthma. Data was extracted by one reviewer. Results Five studies met the inclusion criteria. Methodological quality was variable. There were no trials comparing ciclesonide to beclomethasone. There was no significant difference between ciclesonide and budesonide or fluticasone on the following outcomes: lung function, symptoms, quality of life, airway responsiveness to a provoking agent or inflammatory markers. However, the trials were very small in size, increasing the possibility of a type II error. One trial demonstrated that the combined deposition of ciclesonide (and its active metabolite in the oropharynx was 47% of that of budesonide while another trial demonstrated that the combined deposition of ciclesonide (and its active metabolite in the oropharynx was 53% of that of fluticasone. One trial demonstrated less suppression of cortisol in overnight urine collection after ciclesonide compared to fluticasone (geometric mean fold difference = 1.5, P Conclusion There is very little evidence comparing CIC to other ICS, restricted to very small, phase II studies of low

  5. Compared biokinetic and biological studies of chronic and acute inhalations of uranium compounds in the rat; Etudes biocinetique et biologique comparees d'inhalations chroniques et aigues de composes uraniferes chez le rat

    Energy Technology Data Exchange (ETDEWEB)

    Monleau, M

    2005-12-15

    Uranium is a natural, radioactive heavy metal, widely used in the nuclear industry in various chemical and isotopic forms. Its use in the fuel cycle involves the risk of radiological exposure for the workers, mainly via the inhalation of uranium particles. According to the workplace configuration, uranium contaminations can be acute or repeated, involve various chemical forms and different levels of enrichment, as well as involving one or several components. The dosimetric concepts and models available for workers' radiological protection, as well as most of the studies of the biological effects, correspond to acute exposure situations. Moreover the processes leading to pathological effects are little known in vivo. In this context, the main question is to know whether exposures due to repeated inhalation by rats induce the element kinetics and toxicity, which may be different from those observed after an acute exposure. In this study, comparison of the experimental and theoretical biokinetics of an insoluble uranium repeatedly inhaled over three weeks shows that a chronic contamination is correctly modelled, except for bone retention, by the sum of acute, successive and independent incorporations. Moreover, the kinetics of a soluble uranium inhaled irregularly can be modified by previous repeated exposure to an insoluble uranium. In certain cases therefore, exposure to uranium could modify its biokinetics during later exposures. At a toxicological level, the study demonstrates that the uranium particles inhaled repeatedly induce behavioural disruptions and genotoxic effects resulting in various sorts of DNA damage, in several cell types and certainly depending on the quantity inhaled. Exposures involving several uraniferous components produce a synergy effect. Moreover, repeated inhalations worsen the genotoxic effects in comparison to an acute exposure. This work demonstrates the importance of not ignoring the effects of the repetition of uranium exposure. It

  6. Compared biokinetic and biological studies of chronic and acute inhalations of uranium compounds in the rat; Etudes biocinetique et biologique comparees d'inhalations chroniques et aigues de composes uraniferes chez le rat

    Energy Technology Data Exchange (ETDEWEB)

    Monleau, M

    2005-12-15

    Uranium is a natural, radioactive heavy metal, widely used in the nuclear industry in various chemical and isotopic forms. Its use in the fuel cycle involves the risk of radiological exposure for the workers, mainly via the inhalation of uranium particles. According to the workplace configuration, uranium contaminations can be acute or repeated, involve various chemical forms and different levels of enrichment, as well as involving one or several components. The dosimetric concepts and models available for workers' radiological protection, as well as most of the studies of the biological effects, correspond to acute exposure situations. Moreover the processes leading to pathological effects are little known in vivo. In this context, the main question is to know whether exposures due to repeated inhalation by rats induce the element kinetics and toxicity, which may be different from those observed after an acute exposure. In this study, comparison of the experimental and theoretical biokinetics of an insoluble uranium repeatedly inhaled over three weeks shows that a chronic contamination is correctly modelled, except for bone retention, by the sum of acute, successive and independent incorporations. Moreover, the kinetics of a soluble uranium inhaled irregularly can be modified by previous repeated exposure to an insoluble uranium. In certain cases therefore, exposure to uranium could modify its biokinetics during later exposures. At a toxicological level, the study demonstrates that the uranium particles inhaled repeatedly induce behavioural disruptions and genotoxic effects resulting in various sorts of DNA damage, in several cell types and certainly depending on the quantity inhaled. Exposures involving several uraniferous components produce a synergy effect. Moreover, repeated inhalations worsen the genotoxic effects in comparison to an acute exposure. This work demonstrates the importance of not ignoring the effects of the repetition of uranium exposure

  7. Experimental study of inhalation injury

    International Nuclear Information System (INIS)

    Hamamoto, Junji; Ohura, Takehiko; Yoshida, Tetsunori; Ono, Ichiro; Iida, Kazunori; Ooiwa, Akira

    1984-01-01

    We conducted the following inhalation injury experiment on dogs. A hose was connected to the chimney of a stove so that wood smoke could be led to the dog by means of damper adjustment. Under intravenous anesthesia, the dog was intubated and made to inhale the wood smoke for from 5 to 10 minutes at a smoke temperature of between 55 and 60 C. After this inhalation, observation of trachea by a fiberoptic bronchoscopy was done and blood gas change, blood analysis, serum electrolytes and cardiac output were observed with a passage of time. Furthermore, we did lung scan using 133xe and performed autopsies. We injected 0.3 microcurie of 133Xe per 1 kg body weight in its vein of the dog's foreleg. The concentration in the lung reached maximum 20 seconds after the injection and then washed out with expiration. In the control experiment with a normal dog, it was almost all washed out 70 seconds after the 133Xe injection. But the delay of wash out time was observed in smoke inhaled dogs. In other words it can be said that the wash out time was dependent on the degree of injury. When these data were processed by a computer, and exponential approximation decay curve was obtained. Then these data were replotted into semi-logarithmic chart and a linear line was obtained. One may interprete the clearance rate recorded on the graph as the ability of the lung to wash out 133Xe, that is, the degree of injury of the lung. The clearance rate had a tendancy to concentrate between 3.5 to 5.0 when observed 2 to 7 hours after the injury. However when observed 20 to 27 hours, concentration was between 2.4 to 3.2. Furthermore, the clearance rate for each lung regions were obtained and compared with one another by means of proper computer program. The clearance rate had lower values at lower region of lung, that is, deterioration of lung function was greater. (J.P.N.)

  8. Predictive Toxicology: Current Status and Future Outlook (EBI ...

    Science.gov (United States)

    Slide presentation at the EBI-EMBL Industry Programme Workshop on Predictive Toxicology and the currently status of Computational Toxicology activities at the US EPA. Slide presentation at the EBI-EMBL Industry Programme Workshop on Predictive Toxicology and the currently status of Computational Toxicology activities at the US EPA.

  9. Principles and procedures in forensic toxicology.

    Science.gov (United States)

    Wyman, John F

    2012-09-01

    The principles and procedures employed in a modern forensic toxicology lab are detailed in this review. Aspects of Behavioral and Postmortem toxicology, including certification of analysts and accreditation of labs, chain of custody requirements, typical testing services provided, rationale for specimen selection, and principles of quality assurance are discussed. Interpretation of toxicology results in postmortem specimens requires the toxicologist and pathologist to be cognizant of drug-drug interactions, drug polymorphisms and pharmacogenomics, the gross signs of toxic pathology, postmortem redistribution, confirmation of systemic toxicity in suspected overdoses, the possibility of developed tolerance, and the effects of decomposition on drug concentration.

  10. Toxicology of plutonium-sodium

    International Nuclear Information System (INIS)

    Hackett, P.L.

    1982-01-01

    Scenarios for liquid-metal fast breeder reactor (LMFBR) accidents predict the loss of sodium coolant, with subsequent core melt-down and release of mixed sodium-fuel aerosols [Na-(PuU)O 2 ] into the environment. Studies in other laboratories demonstrated that mixed aerosols of Na 2 O-PuO 2 were more readily transported from the lung than PuO 2 aerosols. We therefore devised a continuous aerosol-generating system for animal exposures in which laser-generated fuel aerosols were swept through sodium vapor to form sodium-fuel aerosols. These fuel and sodium-fuel aerosols were compared with regard to their physicochemical properties and their biological behavior following inhalation studies in rats and dogs

  11. Assessment of the potential for long-term toxicological effects of the Exxon Valdez oil spill on birds and mammals

    International Nuclear Information System (INIS)

    Hartung, R.

    1995-01-01

    This paper assesses the potential for direct long-term toxicological effects of exposures to oils in birds and mammals by tracing exposures and effects form the initial cute phases through the sub-chronic to the eventual long-term exposures. The immediate effects of oil spills are physical, the oil acting on the plumage of birds or the fur of mammals. This causes a loss of entrained air and a concomitant reduction in buoyancy and thermal insulation. Animals that escape the immediate impacts may be isolated from their food supply and often ingest large amounts of oil while attempting to clean themselves. At the comparatively high dose levels involved, these exposures can result in toxicologically significant responses in many organ systems. In the course of an oil pollution incident, the amounts of biologically available oils decrease steadily, and simultaneously the composition of the oils shifts towards those components that have low volatility, and that resist photo- and bio-degradation. As this occurs, the primary pathways of exposure change from direct intakes to indirect routes involving the food supply. Although laboratory studies often report finding some adverse effects, the dose rates employed in many of these studies are extremely high when compared with those that are potentially available to animals in the wild, and very few actually use weathered oils. An assessment of the toxicological literature and of the available empirical data on the Exxon Valdez oil spill leads to the conclusion that long-term sub-lethal toxic effects of crude oils on wildlife in such marine spills appear to be very unlikely. 111 refs., 4 figs., 1 tab

  12. Toxicological Investigation of Acute Carbon Monoxide Poisoning in Four Occupants of a Fuming Sport Utility Vehicle

    Directory of Open Access Journals (Sweden)

    Martin Nnoli

    2014-11-01

    Full Text Available Background: This toxicological investigation involves a report on the death of four occupants of a sport utility vehicle on one of the major busy Federal roads of Nigeria where they were held for up to three hours in a traffic jam while the car was steaming. Methods: Autopsy was executed using the standard procedure and toxicological analysis was done using simple spectrophotometric method to establish the level of carboxyhaemoglobin (HbCO in peripheral blood in the four occupants. Results: The autopsy report indicated generalized cyanosis, sub-conjuctival hemorrhages, marked laryngo-trachea edema with severe hyperemia with frothy fluid discharges characteristic of carbon monoxide poisoning. Toxicological report of the level of HbCO in part per million (ppm in the peripheral blood of the four occupants was A= 650 ppm; B= 500 ppm; C= 480 ppm, and D= 495 ppm against the maximum permissible level of 50 ppm. Conclusion: The sudden death of the four occupants was due to excessive inhalation of the carbon monoxide gas from the exhaust fumes leaking into the cabin of the car. The poor road network, numerous potholes, and traffic jam in most of roads in Nigeria could have exacerbated a leaky exhaust of the smoky second hand SUV car leading to the acute carbon monoxide poisoning.

  13. Developmental toxicology of radon exposures

    International Nuclear Information System (INIS)

    Sikov, M.R.; Cross, F.T.; Mast, T.J.; Palmer, H.E.; James, A.C.; Thrall, K.D.

    1992-01-01

    Concerns about hazards associated with radon exposure in dwellings may be especially relevant to pregnant women, many of whom spend substantial amounts of time in their homes. There are few data concerning the placental transfer and fetoplacental distribution of inhaled radon and decay products or their effects on the conceptus. We performed a study in rats to determine if prenatal effects could be produced by prolonged inhalation exposures to high concentrations of radon throughout gestation. A group of 43 pregnant rats was exposed 18 h d -1 , at a rate of 124 working level months (WLM) per day, from 6 to 19 days of gestation (dg), of radon and daughters adsorbed onto ore dust. A group of 26 pregnant rats from the same shipment was exposed to a filtered-air atmosphere as controls. At 20 dg, the rats were removed from the chambers, killed, and necropsied. The fetuses were evaluated for the presence of toxic effects, which included detailed teratology protocols. These exposures did not produce detectable reproductive toxicity nor teratogenic change. Two other rats were removed from the radon chambers during the last day of exposure, and their tissues were analyzed to determine the distribution of radioactivity and for dosimetry. Samples from these rats suggested that the dose rates to the placenta were roughly threefold those to the fetus but were similar to those to the liver and femur of the pregnant rats. These data indicate that the dose to the conceptus from the decay of placentally transferred radon and its progeny is more important than the contribution of translocated decay products. Translocated radon decay products are an important source of radiation doses to placental structures, however, and may have most of the radioactivity content at birth

  14. Developmental sub-chronic exposure to chlorpyrifos reduces anxiety-related behavior in zebrafish larvae

    Science.gov (United States)

    Richendrfer, Holly; Pelkowski, Sean D.; Colwill, Ruth M.; Créton, Robbert

    2013-01-01

    Neurobehavioral disorders such as anxiety, autism, and attention deficit hyperactivity disorders are typically influenced by genetic and environmental factors. Although several genetic risk factors have been identified in recent years, little is known about the environmental factors that either cause neurobehavioral disorders or contribute to their progression in genetically predisposed individuals. One environmental factor that has raised concerns is chlorpyrifos, an organophosphate pesticide that is widely used in agriculture and is found ubiquitously in the environment. In the present study, we examined the effects of sub-chronic chlorpyrifos exposure on anxiety-related behavior during development using zebrafish larvae. We found that sub-chronic exposure to 0.01 or 0.1 μM chlorpyrifos during development induces specific behavioral defects in 7-day-old zebrafish larvae. The larvae displayed decreases in swim speed and thigmotaxis, yet no changes in avoidance behavior were seen. Exposure to 0.001 μM chlorpyrifos did not affect swimming, thigmotaxis, or avoidance behavior and exposure to 1 μM chlorpyrifos induced behavioral defects, but also induced defects in larval morphology. Since thigmotaxis, a preference for the edge, is an anxiety-related behavior in zebrafish larvae, we propose that sub-chronic chlorpyrifos exposure interferes with the development of anxiety-related behaviors. The results of this study provide a good starting point for examination of the molecular, cellular, developmental, and neural mechanisms that are affected by environmentally relevant concentrations of organophosphate pesticides. A more detailed understanding of these mechanisms is important for the development of predictive models and refined health policies to prevent toxicant-induced neurobehavioral disorders. PMID:22579535

  15. Subchronic effects of valproic acid on gene expression profiles for lipid metabolism in mouse liver

    International Nuclear Information System (INIS)

    Lee, Min-Ho; Kim, Mingoo; Lee, Byung-Hoon; Kim, Ju-Han; Kang, Kyung-Sun; Kim, Hyung-Lae; Yoon, Byung-Il; Chung, Heekyoung; Kong, Gu; Lee, Mi-Ock

    2008-01-01

    Valproic acid (VPA) is used clinically to treat epilepsy, however it induces hepatotoxicity such as microvesicular steatosis. Acute hepatotoxicity of VPA has been well documented by biochemical studies and microarray analysis, but little is known about the chronic effects of VPA in the liver. In the present investigation, we profiled gene expression patterns in the mouse liver after subchronic treatment with VPA. VPA was administered orally at a dose of 100 mg/kg/day or 500 mg/kg/day to ICR mice, and the livers were obtained after 1, 2, or 4 weeks. The activities of serum liver enzymes did not change, whereas triglyceride concentration increased significantly. Microarray analysis revealed that 1325 genes of a set of 32,996 individual genes were VPA responsive when examined by two-way ANOVA (P 1.5). Consistent with our previous results obtained using an acute VPA exposure model (Lee et al., Toxicol Appl Pharmacol. 220:45-59, 2007), the most significantly over-represented biological terms for these genes included lipid, fatty acid, and steroid metabolism. Biological pathway analysis suggests that the genes responsible for increased biosynthesis of cholesterol and triglyceride, and for decreased fatty acid β-oxidation contribute to the abnormalities in lipid metabolism induced by subchronic VPA treatment. A comparison of the VPA-responsive genes in the acute and subchronic models extracted 15 commonly altered genes, such as Cyp4a14 and Adpn, which may have predictive power to distinguish the mode of action of hepatotoxicants. Our data provide a better understanding of the molecular mechanisms of VPA-induced hepatotoxicity and useful information to predict steatogenic hepatotoxicity

  16. Inhalation toxicity of methanol/gasoline in rats: effects of 13-week exposure.

    Science.gov (United States)

    Poon, R; Park, G; Viau, C; Chu, I; Potvin, M; Vincent, R; Valli, V

    1998-01-01

    The subchronic inhalation toxicity of a methanol/gasoline blend (85% methanol, 15% gasoline, v/v) was studied in rats. Sprague Dawley rats (10 animals per group) of both sexes were exposed to vapours of methanol/gasoline at 50/3, 500/30 and 5000/300ppm for 6 hours per day, 5 days per week, for 13 weeks. Control animals inhaled filtered room air only. Control recovery and high dose recovery groups were also included which inhaled room air for an extra 4 weeks following the treatment period. No clinical signs of toxicity were observed in the treatment group and their growth curves were not significantly different from the control. Except for decreased forelimb grip strength in high dose females, no treatment-related neurobehavioural effects (4-6 hours post inhalation) were observed using screening tests which included cage-side observations, righting reflex, open field activities, and forelimb and hindlimb grip strength. At necropsy, the organ to body weight ratios for the liver, spleen, testes, thymus and lungs were not significantly different from the control group. There were no treatment-related effects in the hematological endpoints and no elevation in serum formate levels. Minimal serum biochemical changes were observed with the only treatment-related change being the decreased creatinine in the females. A dose-related increase in urinary ascorbic acid was detected in males after 2, 4 and 8 weeks of exposure, but not after the 12th week, and in females only at week-2. Increased urinary albumin was observed in treated males starting at the lowest dose and at all exposure periods, but not in females. A treatment-related increase in urinary beta 2-microglobulin was detected in males at week-2 only. Except for mild to moderate mucous cell metaplasia in nasal septum B, which occurred more often and with a slightly higher degree of severity in the low dose groups of both sexes, and presence of a minimal degree of interstitial lymphocyte infiltration in the prostate

  17. Multiscale Toxicology- Building the Next Generation Tools for Toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Retterer, S. T. [ORNL; Holsapple, M. P. [Battelle Memorial Institute

    2013-10-31

    A Cooperative Research and Development Agreement (CRADA) was established between Battelle Memorial Institute (BMI), Pacific Northwest National Laboratory (PNNL), Oak Ridge National Laboratory (ORNL), Brookhaven National Laboratory (BNL), Lawrence Livermore National Laboratory (LLNL) with the goal of combining the analytical and synthetic strengths of the National Laboratories with BMI's expertise in basic and translational medical research to develop a collaborative pipeline and suite of high throughput and imaging technologies that could be used to provide a more comprehensive understanding of material and drug toxicology in humans. The Multi-Scale Toxicity Initiative (MSTI), consisting of the team members above, was established to coordinate cellular scale, high-throughput in vitro testing, computational modeling and whole animal in vivo toxicology studies between MSTI team members. Development of a common, well-characterized set of materials for testing was identified as a crucial need for the initiative. Two research tracks were established by BMI during the course of the CRADA. The first research track focused on the development of tools and techniques for understanding the toxicity of nanomaterials, specifically inorganic nanoparticles (NPs). ORNL"s work focused primarily on the synthesis, functionalization and characterization of a common set of NPs for dissemination to the participating laboratories. These particles were synthesized to retain the same surface characteristics and size, but to allow visualization using the variety of imaging technologies present across the team. Characterization included the quantitative analysis of physical and chemical properties of the materials as well as the preliminary assessment of NP toxicity using commercially available toxicity screens and emerging optical imaging strategies. Additional efforts examined the development of high-throughput microfluidic and imaging assays for measuring NP uptake, localization, and

  18. Antihyperglycemic and subchronic toxicity study of Moringa stenopetala leaves in mice

    Directory of Open Access Journals (Sweden)

    Tesemma Sileshi

    2014-03-01

    Full Text Available Objective: To evaluate the antihyperglycemic activity and subchronic toxicity of an extract of Moringa stenopetala (M. stenopetala leaves in mice. Methods: Antihyperglycemic activities of various solvent subfractions and chromatographic fractions were investigated in alloxan induced diabetic mice. All fractions were administered intragastrically using oral gavage at a dose of 500 mg/kg. For the subchronic toxicity investigation of the 70% ethanol extract of M. stenopetala leaves, a daily dose of 300 or 600 mg/kg body weight was administered to mice over 96 d. Some hematological and plasma biochemical parameters were measured as indices of organ specific toxicity. Preliminary phytochemical screening and antioxidant activity investigation was done using thin layer chromatography method. Results: Among the solvent subfractions of the 70% ethanol extract tested only butanol subfraction exhibited significant reduction of blood glucose level (P<0.05 at 2 h (53.44% and 4.5 h (46.34% in diabetic mice and it was further fractionated chromatographically. This resulted in isolation of three chromatographic fractions (fraction 1, 2, and 3 which exhibited maximal blood glucose reduction (P<0.01 at 6 h (77.2%, at 4.5 h (69.1% and at 4.5 h (71.96% after administration. Furthermore, these fractions exhibited comparable antioxidant activity, and preliminary phytochemical screening indicated the presence of phenolic compounds which may be phenolic glycoside in all fractions. The subchronic toxicity study of the 70% ethanol extract of M. stenopetala leaves revealed that there were no significant differences in body weight, between controls and treated mice. Hematological analysis showed no differences in most parameters examined. Furthermore, it did not significantly affect plasma creatinine, urea, cholesterol, triglycerides and CA125 levels. It also did not significantly affect the plasma T3, T4 and THS level. It, however, caused a significant dose

  19. Inhalants

    Science.gov (United States)

    ... most commonly abuse glue, shoe polish, spray paints, gasoline, and lighter fluid. New users ages 16–17 ... paint thinners or removers, degreasers, dry- cleaning fluids, gasoline, and lighter fluid  Art or office supply solvents , ...

  20. Inhalants

    Science.gov (United States)

    ... Viral) HIV/AIDS Mental Health Military Opioid Overdose Reversal with Naloxone (Narcan, Evzio) Pain Prevention Recovery Substance ... chest pain, are misused in order to improve sexual pleasure by expanding and relaxing blood vessels. What ...

  1. Potential consequences of yellowcake inhalation

    International Nuclear Information System (INIS)

    Eidson, A.F.; Damon, E.G.; Hahn, F.F.; Pickrell, J.A.; Muggenburg, B.A.

    1988-01-01

    The uranium ore milling process includes dusty operations and workers can be exposed to aerosols of highly concentrated uranium. Measurements made during uranium milling operations were used to predict that, if a worker was not wearing respiratory protection, 0.14-50 μg U/min might be deposited in the respiratory tract, predominantly in the nesopharyngeal compartment. Yellowcake was shown by infrared and solubility measurements to be a highly variable mixture of ammonium diuranate and U 3 O 8 . Biokinetic studies of inhaled yellowcake in beagle dogs showed that the more soluble fraction caused kidney damage. After inhalation of 0.5 mg U/kg body wt of soluble uranium, kidney concentration was 0.3 to 3.5 μg U/g kidney within 4-8 days; and was accompanied by kidney damage. Kidney damage was neither severe nor widespread, and was repaired within 64 days after exposure. The damage seen is due to heavy metal nephrotoxicity of uranium, and not to radiation damage

  2. Inhaler devices - from theory to practice

    DEFF Research Database (Denmark)

    Sanchis, Joaquin; Corrigan, Chris; Levy, Mark L

    2013-01-01

    This brief overview of the factors determining lung deposition of aerosols provides background information required by health care providers when instructing patients to use their prescribed inhalers. We discuss differences in the optimal inhalation manoeuvres for each type of aerosol generator a...

  3. A review of the toxicology and epidemiology of wollastonite.

    Science.gov (United States)

    Maxim, L Daniel; McConnell, E E

    2005-08-01

    Wollastonite is a naturally occurring calcium silicate (CaSiO(3)) that is produced in both powder and fibrous forms. It is a valuable industrial mineral used in plastics, ceramics, metallurgical applications, paint, and friction products. For some applications wollastonite serves as an asbestos replacement. To varying degrees, wollastonite grades contain respirable particles/fibers, some of which have lengths and diameters that might be biologically active if deposited and retained in the lung. In this review we provide background information on wollastonite properties, markets, production and use, regulatory classification, and occupational exposure limits. We also summarize the available studies on the toxicology and epidemiology of wollastonite. We conclude that there is inadequate evidence for the carcinogenicity of wollastonite in animals and, based on strong evidence that wollastonite is not biopersistent, believe that a well-designed animal inhalation bioassay would have a negative result. The epidemiological evidence for wollastonite is limited, but does not suggest that workers are at significant risk of an increased incidence of pulmonary fibrosis, lung cancer, or mesothelioma. Morbidity studies have demonstrated a nonspecific increase in bronchitis and reduced lung function. It is prudent, however, to continue product stewardship efforts by wollastonite producers to control workplace exposures and to monitor scientific developments.

  4. [New toxicological patterns of nanomaterials, nanostructures and nanoparticles].

    Science.gov (United States)

    Mazzotta, M; Mazzotta, A D; Fernández, M; Tamborino, B; De Filippis, G

    2012-01-01

    Nanomaterials engineered as nanotubes, quantum-dots, dendrimers or hybrid systems are increasing themselves by an annual mean rate of 4-5%, with rapid spread in various sectors e.g. biomedical. The liposolubility through membranes and the hydrosolubility through active transport do not interfere with nanoparticles below a certain size, which without activation processes and carrier, transport through thanks to capillaries, to intracellular pores (60 - 70 nm) and fissures (4 - 6 nm) in the same membranes. Conversely, in the processes of pinocytosis/endocytosis energy and carrier are required and endocytosis clathrin/caveolae mediated,is respectively for nanoparticles higher or lower than 200 nm. In occupational hazard nanostructures ranging from a few nm up to 100 - 150 nm have the ability to affect several organs through inhalation, intestinal, parental or dermal route of access. New toxicological aspects are associated to the capacity of nanomaterials of being more or less biocompatible or hydrosoluble, of creating bonds with proteins or to determine accumulation in the cells due to an incomplete elimination process.

  5. Techniques for Investigating Molecular Toxicology of Nanomaterials.

    Science.gov (United States)

    Wang, Yanli; Li, Chenchen; Yao, Chenjie; Ding, Lin; Lei, Zhendong; Wu, Minghong

    2016-06-01

    Nanotechnology has been a rapidly developing field in the past few decades, resulting in the more and more exposure of nanomaterials to human. The increased applications of nanomaterials for industrial, commercial and life purposes, such as fillers, catalysts, semiconductors, paints, cosmetic additives and drug carriers, have caused both obvious and potential impacts on human health and environment. Nanotoxicology is used to study the safety of nanomaterials and has grown at the historic moment. Molecular toxicology is a new subdiscipline to study the interactions and impacts of materials at the molecular level. To better understand the relationship between the molecular toxicology and nanomaterials, this review summarizes the typical techniques and methods in molecular toxicology which are applied when investigating the toxicology of nanomaterials and include six categories: namely; genetic mutation detection, gene expression analysis, DNA damage detection, chromosomal aberration analysis, proteomics, and metabolomics. Each category involves several experimental techniques and methods.

  6. Comparative BioInformatics and Computational Toxicology

    Science.gov (United States)

    Reflecting the numerous changes in the field since the publication of the previous edition, this third edition of Developmental Toxicology focuses on the mechanisms of developmental toxicity and incorporates current technologies for testing in the risk assessment process.

  7. Environmental chemistry and toxicology of mercury

    National Research Council Canada - National Science Library

    Liu, Guangliang; Cai, Yong; O'Driscoll, Nelson J

    2012-01-01

    ... employed in recent studies. The coverage discusses the environmental behavior and toxicological effects of mercury on organisms, including humans, and provides case studies at the end of each chapter...

  8. IRIS Toxicological Review of Chloroform (Final Report)

    Science.gov (United States)

    EPA is announcing the release of the final report, Toxicological Review of Chloroform: in support of the Integrated Risk Information System (IRIS). The updated Summary for Chloroform and accompanying Quickview have also been added to the IRIS Database.

  9. Multiscale Toxicology - Building the Next Generation Tools for Toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Thrall, Brian D.; Minard, Kevin R.; Teeguarden, Justin G.; Waters, Katrina M.

    2012-09-01

    A Cooperative Research and Development Agreement (CRADA) was sponsored by Battelle Memorial Institute (Battelle, Columbus), to initiate a collaborative research program across multiple Department of Energy (DOE) National Laboratories aimed at developing a suite of new capabilities for predictive toxicology. Predicting the potential toxicity of emerging classes of engineered nanomaterials was chosen as one of two focusing problems for this program. PNNL’s focus toward this broader goal was to refine and apply experimental and computational tools needed to provide quantitative understanding of nanoparticle dosimetry for in vitro cell culture systems, which is necessary for comparative risk estimates for different nanomaterials or biological systems. Research conducted using lung epithelial and macrophage cell models successfully adapted magnetic particle detection and fluorescent microscopy technologies to quantify uptake of various forms of engineered nanoparticles, and provided experimental constraints and test datasets for benchmark comparison against results obtained using an in vitro computational dosimetry model, termed the ISSD model. The experimental and computational approaches developed were used to demonstrate how cell dosimetry is applied to aid in interpretation of genomic studies of nanoparticle-mediated biological responses in model cell culture systems. The combined experimental and theoretical approach provides a highly quantitative framework for evaluating relationships between biocompatibility of nanoparticles and their physical form in a controlled manner.

  10. Inhalant Dependence and its Medical Consequences

    Directory of Open Access Journals (Sweden)

    Mehmet Hamid Boztaş

    2010-12-01

    Full Text Available The term of inhalants is used for matters easily vapors. Inhalants are preferred for rapid, positive reinforcement and mild high effects. Products including inhalants are cheap, accessible, legal substances and are prevalently used in community. The prevalence of inhalant use in secondary schools in Turkey is about 5.1%. Inhalant substance dependence is generally observed within 14-15 age group. Age at first use could be as low as 5 to 6 years of age. Substance dependence is more probable in adults working in substance existing places. Inhalant usage is common in disadvantaged groups, children living in street, people with history of crimes, prison, depression, suicide, antisocial attitudes and conflict of family, history of abuse, violence and any other drug dependence and isolated populations. Inhalants are absorbed from lungs, after performing their quick and short effect metabolized by cytochrom P450 enzyme system except inhalant nitrites group which has a depressing effect like alcohol. In chronic use general atrophy, ventricular dilatation and wide sulcus were shown in cerebrum, cerebellum and pons by monitoring brain. Defects are mostly in periventricular, subcortical regions and in white matter. Demyelinization, hyperintensity, callosal slimming and wearing off in white and gray matter margins was also found. Ravages of brain shown by brain monitorisation are more and serious in inhalant dependence than in other dependences. It is important to decrease use of inhalants. Different approaches should be used for subcultures and groups in prevention. Prohibiting all the matters including inhalant is not practical as there are too many substances including inhalants. Etiquettes showing harmful materials can be used but this approach can also lead the children and adolescents recognize these substances easily.. Despite determintal effects of inhalant dependence, there are not yet sufficient number of studies conducted on prevention and

  11. Two-week aerosol inhalation study on polyethylene glycol (PEG) 3350 in F-344 rats.

    Science.gov (United States)

    Klonne, D R; Dodd, D E; Losco, P E; Troup, C M; Tyler, T R

    1989-03-01

    PEGs in the 3000 to 4000 MW range are used in many pharmaceutical and cosmetic applications; they produce little ocular or dermal irritation and have extremely low acute and subchronic toxicity by oral and dermal routes of administration. However, little information exists on the potential of aerosols of these materials to produce adverse health effects. F-344 rats were exposed to aerosols of PEG 3350 (20% w:w in water) at 0, 109, 567, or 1008 (highest attainable) mg/m3 for 6 hr/d, 5 d/wk for 2 wk. No exposure-related toxicity was found with regard to clinical signs, ophthalmology, serum chemistry, urinalysis, or gross pathology. Exposure-related effects included: a 50% increase in the neutrophil count (males only) at 1008 mg/m3; decreased body weight gain (16%) for both the 567 and 1008 mg/m3 groups (males only); absolute lung weights of both sexes were increased 10 and 18% for the 567 and 1008 mg/m3 groups, respectively. A slight increase in the number of macrophages in the alveoli was the only change observed histologically in all PEG 3350-exposed groups. Therefore, inhalation of aerosols of PEG 3350 at concentrations up to 1008 mg/m3 produced relatively little toxicity in rats, the lung was the target organ, and the no-observable-effect-level was between 109 to 567 mg/m3.

  12. In vivo genotoxicity assessment in rats exposed to Prestige-like oil by inhalation.

    Science.gov (United States)

    Valdiglesias, Vanessa; Kiliç, Gözde; Costa, Carla; Amor-Carro, Óscar; Mariñas-Pardo, Luis; Ramos-Barbón, David; Méndez, Josefina; Pásaro, Eduardo; Laffon, Blanca

    2012-01-01

    One of the largest oil spill disasters in recent times was the accident of the oil tanker Prestige in front of the Galician coast in 2002. Thousands of people participated in the cleanup of the contaminated areas, being exposed to a complex mixture of toxic substances. Acute and prolonged respiratory symptoms and genotoxic effects were reported, although environmental exposure measurements were restricted to current determinations, such that attribution of effects observed to oil exposure is difficult to establish. The aim of this study was to analyze peripheral blood leukocytes (PBL) harvested from a rat model of subchronic exposure to a fuel oil with similar characteristics to that spilled by the Prestige tanker, in order to determine potential genotoxic effects under strictly controlled, in vivo exposure. Wistar Han and Brown Norway rats were exposed to the oil for 3 wk, and micronucleus test (MN) and comet assay, standard and modified with 8-oxoguanine DNA glycosylase (OGG1) enzyme, were employed to assess genotoxicity 72 h and 15 d after the last exposure. In addition, the potential effects of oil exposure on DNA repair capacity were determined by means of mutagen sensitivity assay. Results obtained from this study showed that inhalation oil exposure induced DNA damage in both Brown Norway and Wistar Han rats, especially in those animals evaluated 15 d after exposure. Although alterations in the DNA repair responses were noted, the sensitivity to oil substances varied depending on rat strain. Data support previous positive genotoxicity results reported in humans exposed to Prestige oil during cleanup tasks.

  13. Modern Instrumental Methods in Forensic Toxicology*

    Science.gov (United States)

    Smith, Michael L.; Vorce, Shawn P.; Holler, Justin M.; Shimomura, Eric; Magluilo, Joe; Jacobs, Aaron J.; Huestis, Marilyn A.

    2009-01-01

    This article reviews modern analytical instrumentation in forensic toxicology for identification and quantification of drugs and toxins in biological fluids and tissues. A brief description of the theory and inherent strengths and limitations of each methodology is included. The focus is on new technologies that address current analytical limitations. A goal of this review is to encourage innovations to improve our technological capabilities and to encourage use of these analytical techniques in forensic toxicology practice. PMID:17579968

  14. Integrative Systems Biology Applied to Toxicology

    DEFF Research Database (Denmark)

    Kongsbak, Kristine Grønning

    associated with combined exposure to multiple chemicals. Testing all possible combinations of the tens of thousands environmental chemicals is impractical. This PhD project was launched to apply existing computational systems biology methods to toxicological research. In this thesis, I present in three...... of a system thereby suggesting new ways of thinking specific toxicological endpoints. Furthermore, computational methods can serve as valuable input for the hypothesis generating phase of the preparations of a research project....

  15. Toxicological evaluation and metabolism of two N-alkyl benzamide umami flavour compounds: N-(heptan-4-ylbenzo[d][1,3]dioxole-5-carboxamide and (R-N-(1-methoxy-4-methylpentan-2-yl-3,4-dimethylbenzamide

    Directory of Open Access Journals (Sweden)

    Donald S. Karanewsky

    Full Text Available Toxicological evaluations of two N-alkyl benzamide umami flavour compounds, N-(heptan-4-ylbenzo[d][1,3]dioxole-5-carboxamide (S807, CAS 745047-51-2 and (R-N-(1-methoxy-4-methylpentan-2-yl-3,4-dimethylbenzamide (S9229, CAS 851669-60-8, were completed for the purpose of assessing their safety for use in food and beverage applications. Both S807 and S9229 undergo rapid oxidative metabolism by both rat and human liver microsomes in vitro. In pharmacokinetic studies in rats, the systemic exposure to S9229 on oral administration is very low at all doses (% F < 1%, while that of S807 demonstrated a non-linear dose dependence. In metabolism studies in rats, hydroxylation of the C-4 aryl methyl group was found to be the dominant metabolic pathway for S9229. The dominant metabolic pathway for S807 in the rat involved oxidative scission of the methylenedioxy moiety to produce the corresponding 3,4-dihydroxybenamide which is further converted by Phase II metabolic enzymes to the 3- and 4-O-methyl ethers as well as their corresponding glucuronides. Both S807 and S9229 were not found to be mutagenic or clastogenic in vitro, and did not induce micronuclei in polychromatic erythrocytes in vivo. In a subchronic oral toxicity study in rats, the no-observed-effect-level (NOEL for S807 was 20 mg/kg bw/day when administered in the diet for 13 weeks. The no-observed-adverse-effect-level (NOAEL for S9229 in rats was 100 mg/kg bw/day (highest dose tested when administered in the diet for 28 consecutive days. Keywords: S807, S9229, FEMA GRAS, Subchronic toxicological evaluation, Genetic toxicological evaluation

  16. Effect of subchronic administration of nutmeg (Myristica fragrans Houtt) ethanolic extract to hematological parameters in rat

    Science.gov (United States)

    Bachri, M. S.; Yuliani, S.; Sari, A. K.

    2017-11-01

    Nutmeg is dried kernel of broadly ovoid seed of Myristica fragrans Houtt. It has been mentioned in ethnomedical literature as aphrodisiac, stomachic, carminative, tonic, and nervous stimulant. In order to establish the safety of nutmeg, the effect of the repeated administration of nutmeg is needed. The study was aimed to determine the toxic effect of subchronic administration of nutmeg ethanolic extract to hematological parameters in rat. A total of 28 male adult Wistar rats divided into 4 groups. Group I as control was given by 0.5% CMC-suspension, group II, III, and IV were given by 50, 100, and 200 mg/kg bw, respectively, of nutmeg ethanolic extract. The treatments were administered daily for 31 days. On day 31 bloods were taken from orbital sinus. The hematological parameter consisted of the numbers of erythrocyte and leukocyte as well as hemoglobin and total protein levels were measured. The data were statistically analyzed by one way Anova followed by LSD test. All of observed hematological parameters in rats showed that there were no significant difference between the nutmeg ethanolic extract treated groups and control group. The result indicated that the subchronic administration of 50, 100, and 200 mg/kg bw of nutmeg ethanolic extract did not cause the change of hematological parameters in rat.

  17. Acute and subchronic toxicity studies of methanol extract of Polygonum minus leaves in Sprague Dawley rats.

    Science.gov (United States)

    Christapher, Parayil Varghese; Parasuraman, Subramani; Asmawi, Mohd Zaini; Murugaiyah, Vikneswaran

    2017-06-01

    Medicinal plant preparations may contain high levels of toxic chemical constituents to potentially cause serious harm to animals and/or humans. Thus, toxicity studies are important to assess the toxic effects of plant derived products. Polygonum minus is used traditionally for different ailments in Southeast Asia. This study was conducted to establish the acute and subchronic toxicity profile of the methanol extract of P. minus leaves. The acute toxicity study showed that the methanol extract of P. minus is safe even at the highest dose tested of 2000 mg/kg in female Sprague Dawley rats. There were no behavioural or physiological changes and gross pathological abnormalities observed. The subchronic toxicity study of methanol extract of P. minus at 250, 500, 1000 and 2000 mg/kg were conducted in both sexes of Sprague Dawley rats. There were no changes observed in the extract treated animal's body weight, food and water intake, motor coordination, behaviour and mental alertness. The values of haematological and biochemical parameters were not different between the treated and control animals. The relative organ weights of extract-treated animals did not differ with that of control animals. Based on the present findings, the methanol extract of P. minus leaves could be considered safe up to the dose of 2000 mg/kg. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Acute and subchronic effects of Org 2305 and diazepam on psychomotor performance in man.

    Science.gov (United States)

    Mattila, M J; Koski, J; Strömberg, C

    1987-02-01

    Three doses (15, 30 and 60 mg) of Org 2305 (O 15, O 30 and O 60 respectively), a novel anxiolytic drug chemically related to mianserin, were compared with placebo and 15 mg diazepam (DZ) on human psychomotor performance in a double-blind, cross-over study with 15 healthy volunteers. Objective measurements (choice reaction, tracking, flicker fusion, Maddox wing, digit symbol substitution, memory recall) and subjective assessments (visual analogue scales) were done at baseline and 2 and 13 h after the first dose. This testing procedure was repeated on day 7 when administering the seventh consecutive daily night-time dose. After the first dose O 15 did not differ from placebo and O 30 rarely differed from placebo. O 60 impaired various objective functions similarly to, or less than DZ. Subjectively, DZ and O 60 were felt as sedative. During subchronic treatment, DZ caused some impairment of baseline due to accumulation of bioassayable benzodiazepines, but significant responses to the last DZ dose were less than those to the first dose. DZ but not O 60 was reported to have caused lethargy and clumsiness during subchronic treatment. In the doses used Org 2305 impaired psychomotor performance less than diazepam did. A dose of 60 mg Org 2305 may offer some advantage over 15 mg diazepam, provided that their anxiolytic effects are about similar.

  19. Acute and subchronic toxicity studies of the original drug FS-1

    Directory of Open Access Journals (Sweden)

    Assem Kalykova

    2016-01-01

    Full Text Available Interest in iodine complexes has increased significantly in recent years because of their wide spectrum of biological activity. The FS-1 is an ion nanostructured complex formed by proteins and/or polypeptides, carbohydrates, salts of alkali and alkaline earth metals with intercalated iodine. Patented in 2014, it is intended for the treatment of infectious diseases of bacterial origin including nosocomial infections and multidrug resistant tuberculosis. The aim of the study was to determine its acute and subchronic toxicity. The study of acute and subchronic toxicity was performed on adult Wistar rats according to OECD guidelines. The data on acute toxicity showed LD50 > 2,000 mg/kg after a single intragastric administration. Twenty-eight days of FS-1 administration at a dose of 500 mg/kg resulted in toxic effects. At a dose of 250 mg/kg, the toxic effects were temporary and a return to normal followed after the recovery period. Doses of 100 mg/kg had no adverse effects on the rats.

  20. Sub-chronic exposure to paraoxon neither induces nor exacerbates diabetes mellitus in Wistar rat.

    Science.gov (United States)

    Nurulain, Syed M; Petroianu, Georg; Shafiullah, Mohamed; Kalász, Huba; Oz, Murat; Saeed, Tariq; Adem, Abdu; Adeghate, Ernest

    2013-10-01

    There is an increasing belief that organophosphorus compounds (OPCs) impair glucose homeostasis and cause hyperglycemia and diabetes mellitus. The present study was undertaken to investigate the putative diabetogenic effect of sub-lethal and sub-chronic exposure to paraoxon (POX), an extremely hazardous OPC used in pesticides. The effect of paraoxon on streptozotocin-induced diabetic rats was also examined. Each rat was injected with 100 nmol of POX 5 days per week for 6 weeks. Blood glucose levels and red blood cell acetylcholinesterase activity were measured weekly. Biochemical analysis and morphological studies were performed at the end of the experiment. The results revealed that POX neither induces nor exacerbates diabetes mellitus in experimental rats. Liver and kidney/body weight ratios revealed statistically insignificant differences when compared with controls. Biochemical analysis of urine samples showed a small but not significant increase in protein level in all groups. Urine bilirubin was significantly higher in the diabetes + POX group when compared with the control group. The number of blood cells in urine was significantly higher in the POX-treated group compared with the control group. Hyperglycemia was noted in the diabetes and diabetes + POX groups, but neither in the saline control nor in POX-treated normal rats. Electron microscopy of POX-treated pancreas did not show any morphological changes in beta cells. These results suggest that POX does not cause diabetes mellitus at sub-lethal sub-chronic exposure. Copyright © 2012 John Wiley & Sons, Ltd.

  1. Acute and subchronic toxicity assessment model of Ferula assa-foetida gum in rodents

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    Ayman Goudah

    2015-05-01

    Full Text Available Aim: The present study was performed to investigate acute and subchronic oral toxicity of Ferula assa-foetida gum (28 days in Sprague Dawley rats. Materials and Methods: Acute oral administration of F. assa-foetida was done as a single bolus dose up to 5 g/kg in mice and subchronic toxicity study for 28 days was done by oral administration at doses of 0 (control and 250 mg/kg in Sprague Dawley rats. Results: The obtained data revealed that oral administration of F. assa-foetida extract in rats for 28 successive days had no significant changes on body weight, body weight gain, the hematological parameters in rats all over the period of the experiment, and there are no significant increases in the activity of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine and urea. Liver of treated rats showed mild changes as thrombosis and sinusoidal leukocytosis. It also showed portal infiltration with inflammatory cells, while kidney of treated rat showed an atrophy of glomerular tuft, thickening of parietal layer of Bowman capsule, and focal tubular necrosis. It also showed dilatation and congestion of renal blood vessels. Conclusion: We concluded that F. assa-foetida gum had broad safety and little toxicity for short term use in dose of 250 mg/kg.

  2. Acute and subchronic toxicity assessment model of Ferula assa-foetida gum in rodents.

    Science.gov (United States)

    Goudah, Ayman; Abdo-El-Sooud, Khaled; Yousef, Manal A

    2015-05-01

    The present study was performed to investigate acute and subchronic oral toxicity of Ferula assa-foetida gum (28 days) in Sprague Dawley rats. Acute oral administration of F. assa-foetida was done as a single bolus dose up to 5 g/kg in mice and subchronic toxicity study for 28 days was done by oral administration at doses of 0 (control) and 250 mg/kg in Sprague Dawley rats. The obtained data revealed that oral administration of F. assa-foetida extract in rats for 28 successive days had no significant changes on body weight, body weight gain, the hematological parameters in rats all over the period of the experiment, and there are no significant increases in the activity of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine and urea. Liver of treated rats showed mild changes as thrombosis and sinusoidal leukocytosis. It also showed portal infiltration with inflammatory cells, while kidney of treated rat showed an atrophy of glomerular tuft, thickening of parietal layer of Bowman capsule, and focal tubular necrosis. It also showed dilatation and congestion of renal blood vessels. We concluded that F. assa-foetida gum had broad safety and little toxicity for short term use in dose of 250 mg/kg.

  3. Acute and Subchronic Toxic Effects of the Fruits of Physalis peruviana L.

    Directory of Open Access Journals (Sweden)

    Basak Ozlem Perk

    2013-01-01

    Full Text Available The fruit of Physalis peruviana L. (PPL has been traditionally used as antispasmodic, diuretic, antiseptic, sedative, and analgesic all over the world. We aimed to perform qualitative content analysis of the fruits of PPL and to clarify the in vitro genotoxicity and in vivo acute and subchronic toxicity of the fruit. Lyophilized fruit juice does not induce genetic damage. In the acute toxicity studies, LD50 value of the fruit was found to be more than 5000 mg kg−1 for both sexes. According to the subchronic toxicity studies, hepatic, renal, and hematological toxic effects were not induced in both sexes. Plasma troponin I (only in the group treated with 5000 mg kg−1 of lyophilized fruit juice and troponin T levels were significantly increased in male groups treated with lyophilized fruit juice compared to the control group. Furthermore, potassium level was significantly increased in the male group treated with 5000 mg kg−1 of lyophilized fruit juice. These findings were considered to indicate the myocardial damage particularly in the male group treated with 5000 mg kg−1 of lyophilized fruit juice. In conclusion, lyophilized fruit juice of PPL is shown to induce cardiac toxicity only at high doses and in male gender.

  4. Acute and Subchronic Toxic Effects of the Fruits of Physalis peruviana L.

    Science.gov (United States)

    Perk, Basak Ozlem; Ilgin, Sinem; Atli, Ozlem; Duymus, Hale Gamze; Sirmagul, Basar

    2013-01-01

    The fruit of Physalis peruviana L. (PPL) has been traditionally used as antispasmodic, diuretic, antiseptic, sedative, and analgesic all over the world. We aimed to perform qualitative content analysis of the fruits of PPL and to clarify the in vitro genotoxicity and in vivo acute and subchronic toxicity of the fruit. Lyophilized fruit juice does not induce genetic damage. In the acute toxicity studies, LD50 value of the fruit was found to be more than 5000 mg kg(-1) for both sexes. According to the subchronic toxicity studies, hepatic, renal, and hematological toxic effects were not induced in both sexes. Plasma troponin I (only in the group treated with 5000 mg kg(-1) of lyophilized fruit juice) and troponin T levels were significantly increased in male groups treated with lyophilized fruit juice compared to the control group. Furthermore, potassium level was significantly increased in the male group treated with 5000 mg kg(-1) of lyophilized fruit juice. These findings were considered to indicate the myocardial damage particularly in the male group treated with 5000 mg kg(-1) of lyophilized fruit juice. In conclusion, lyophilized fruit juice of PPL is shown to induce cardiac toxicity only at high doses and in male gender.

  5. [Toxicological evaluation in the childhood].

    Science.gov (United States)

    Arroyo, Amparo; Rodrigo, Carlos; Marrón, M Teresa

    2014-03-01

    Intoxications in infancy require urgent medical treatment within national health systems. In our country they represent 0.3% of paediatric urgencies. Most of them are accidental intoxications but is not infrequent to find some related to child abuse or to suicidal intentions, especially in adolescence. The objectives of the study are to evaluate both clinical health care and medical legal aspects in intoxications in infancy. Medical assistance is described and it includes clinical diagnosis, typology of the more common toxics, percentages and referral to social work and emergency care equipment units of the Ministry of Social Welfare and the Department of Health or, where appropriate, directly to prosecutors and courts for their intervention. In cases of detection of alcohol, drugs or medication in infants, the importance of the correct interpretation of the results of toxicological findings is discussed. Several studies for the interpretation of results concerning the detection of these toxics are reported. Both legal aspects and the forensic medical opinion are assessed. The findings will be analysed by the judicial authority in order to circumscribe responsibilities or to take appropriate decisions concerning the protection of infants' interests. In conclusion intoxication in infancy can lead to legal proceedings requiring specific actions for their protection. Both physicians and hospitals must comply with the legal requirement of the submission to the court of judicial parties. On the other hand, this information is an interesting step toward reinforcing public health surveillance. Copyright © 2014 Elsevier España, S.L. All rights reserved.

  6. Good Practices in Forensic Toxicology.

    Science.gov (United States)

    Drummer, Olaf H

    2017-01-01

    This manuscript provides an overview for analysts, medical and scientific investigators, and laboratory administrators, the range of factors that should be considered to implement best practice forensic toxicology. These include laboratory influence over the collection of specimens, their proper transport and chain-of-custody before arrival in the laboratory. In addition, the laboratory needs to ensure properly trained staff use suitably validated and documented analytical procedures that meet the intended purpose and type of case in an accredited or suitably quality oriented management system. To assist the investigating officers laboratory results require an interpretation over their possible significance when sufficient details are available over the circumstances of the case. This requires a thorough understanding of the various factors that influence concentrations of substances and ultimately their likely physiological effect. These include consideration of the route of ingestion, influence over chronicity of usage on tissue concentrations and tolerance, possible combined drug effects or likely adverse reactions and consideration of relevant genetic factors that may have influenced pharmacokinetic or pharmacodynamic response. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Introduction: biomarkers in neurodevelopment toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Needleman, H.L.

    1987-10-01

    The search for markers of toxicant exposure and effect upon the development of organisms presents a set of challenges that differ in many ways from those encountered in the study of markers in reproduction or pregnancy. These latter two fields specify a relatively narrow set of organs or biological systems. The term development, on the other hand, can apply to any organ system, or to any set of phenomena that changes in an ordered way over time. For this reason the papers presented in the session on development were chosen to narrow the focus to neurodevelopmental markers, as such markers may be altered by neurotoxic exposure. In attempting to meet this task, the authors have been able to select a group of investigators who work at the leading edges of their respective fields of developmental neuroanatomy, neurotoxicology, neuroendocrinology, neuropsychology, and infant development. The notion that toxicants could affect behavior certainly is not new. Recent knowledge that behavioral aberrations can occur at exposures below those which produce organic changes, and that behavioral aberrations can occur at exposures below those which produce organic changes, and that behavioral observation might provide early markers of effect has given rise to two new fields: behavioral toxicology and behavioral teratology.

  8. Inhalation of nanoparticle-based drug for lung cancer treatment: Advantages and challenges

    Directory of Open Access Journals (Sweden)

    Wing-Hin Lee

    2015-12-01

    Full Text Available Ever since the success of developing inhalable insulin, drug delivery via pulmonary administration has become an attractive route to treat chronic diseases. Pulmonary delivery system for nanotechnology is a relatively new concept especially when applicable to lung cancer therapy. Nano-based systems such as liposome, polymeric nanoparticles or micelles are strategically designed to enhance the therapeutic index of anti-cancer drugs through improvement of their bioavailability, stability and residency at targeted lung regions. Along with these benefits, nano-based systems also provide additional diagnostic advantages during lung cancer treatment, including imaging, screening and drug tracking. Nevertheless, delivery of nano-based drugs via pulmonary administration for lung cancer therapy is still in its infancy and numerous challenges are expected. Pharmacology, immunology, toxicology and large-scale manufacturing (stability and activity of drugs are some aspects in nanotechnology that should be taken into consideration for the development of inhalable nano-based chemotherapeutic drugs. This review will focus on the current inhalable nano-based drugs for lung cancer treatment.

  9. Detection of butane gas inhalation at 16days after hypoxic encephalopathy: A case report.

    Science.gov (United States)

    Sato, Takako; Nishioka, Hiroshi; Tsuboi, Kento; Katagi, Munehiro; Miki, Akihiro; Saito, Takashi; Abe, Shuntaro; Nomura, Masakatsu; Kitagawa, Misa; Tsuchihashi, Hitoshi; Suzuki, Koichi

    2017-11-01

    In Japan, there are increasing reports of death by poisoning following butane abuse. To determine the specific cause of death in such cases, it is important to confirm the presence of fuel gas components in the body, although careful analysis is required because of their volatile properties. In most reported cases, the subject died suddenly during or immediately after butane aspiration. Thus, the butane concentration in the samples from the deceased should be relatively high. Herein, we present a case of an 18-year-old man found with cardiopulmonary arrest, who then exhibited hypoxic encephalopathy for 16days in a hospital. At autopsy, we detected hypoxic encephalopathy, pneumonia, and ischemia-reperfusion injury of the myocardium, while the cause of cardiac arrest remained unclear. Toxicological analysis was then performed for fuel gas components in several specimens collected at autopsy. Results showed that n-butane and isobutane were detected in the adipose tissue at 16days after inhalation, indicating a role of butane gas inhalation as the cause of death. These data suggest that adipose tissue may be the most appropriate analysis sample to be collected at postmortem in cases where involvement of volatile and fat-soluble gas inhalation is suspected. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Reactive Periostitis from Inhalant Abuse.

    Science.gov (United States)

    Hock, Lauren E; Honkanen, Iiro; Fiordellisi, Wendy; Bettendorf, Brittany

    2018-04-16

    The patient, a 36-year-old woman, presented with a 6-week history of swollen hands and fingers and associated arthralgia. She had a history of polysubstance abuse. The arthralgia and swelling started one month after she began inhaling two cans of "Dust-Off" (1,1-difluoroethane) daily. Physical examination revealed tender proximal and middle phalanges of all fingers bilaterally with bulbous appearance (A). There was no clubbing. Radiography of the hands revealed diffuse reactive periostitis with discrete layering of periosteal bone formation without bony destruction (B). TSH was normal. Serum alkaline phosphatase was 854 U/L. Computed tomography of the chest, abdomen, and pelvis showed no evidence of malignancy or pulmonary disease This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  11. [Methemoglobinemia after inhalation of poppers].

    Science.gov (United States)

    Janssens, U; Hillen, S; Janssens, T; Grafe, J

    2018-04-17

    This case report presents a case of symptomatic methemoglobinemia (MetHb 31.6%) after inhalation of volatile nitrites (poppers). The patient's medical history and symptoms are discussed together with pathophysiology of methemoglobinemia, diagnostics, and antidote therapy. Pulse oxymetry, arterial blood gas analysis, and CO-oximetry receive particular attention as well as antidote therapy with methylene blue. The patient was treated successfully with intravenous methylene blue. Within 60 min methemoglobinemia returned to normal values (MetHb 0.6%). Stimulating compounds such as volatile nitrites (poppers) may lead to potentially fatal methemoglobinemia. Swift and accurate diagnosis and targeted therapy with methylene blue can lead to rapid recovery.

  12. Data governance in predictive toxicology: A review.

    Science.gov (United States)

    Fu, Xin; Wojak, Anna; Neagu, Daniel; Ridley, Mick; Travis, Kim

    2011-07-13

    Due to recent advances in data storage and sharing for further data processing in predictive toxicology, there is an increasing need for flexible data representations, secure and consistent data curation and automated data quality checking. Toxicity prediction involves multidisciplinary data. There are hundreds of collections of chemical, biological and toxicological data that are widely dispersed, mostly in the open literature, professional research bodies and commercial companies. In order to better manage and make full use of such large amount of toxicity data, there is a trend to develop functionalities aiming towards data governance in predictive toxicology to formalise a set of processes to guarantee high data quality and better data management. In this paper, data quality mainly refers in a data storage sense (e.g. accuracy, completeness and integrity) and not in a toxicological sense (e.g. the quality of experimental results). This paper reviews seven widely used predictive toxicology data sources and applications, with a particular focus on their data governance aspects, including: data accuracy, data completeness, data integrity, metadata and its management, data availability and data authorisation. This review reveals the current problems (e.g. lack of systematic and standard measures of data quality) and desirable needs (e.g. better management and further use of captured metadata and the development of flexible multi-level user access authorisation schemas) of predictive toxicology data sources development. The analytical results will help to address a significant gap in toxicology data quality assessment and lead to the development of novel frameworks for predictive toxicology data and model governance. While the discussed public data sources are well developed, there nevertheless remain some gaps in the development of a data governance framework to support predictive toxicology. In this paper, data governance is identified as the new challenge in

  13. Data governance in predictive toxicology: A review

    Directory of Open Access Journals (Sweden)

    Fu Xin

    2011-07-01

    Full Text Available Abstract Background Due to recent advances in data storage and sharing for further data processing in predictive toxicology, there is an increasing need for flexible data representations, secure and consistent data curation and automated data quality checking. Toxicity prediction involves multidisciplinary data. There are hundreds of collections of chemical, biological and toxicological data that are widely dispersed, mostly in the open literature, professional research bodies and commercial companies. In order to better manage and make full use of such large amount of toxicity data, there is a trend to develop functionalities aiming towards data governance in predictive toxicology to formalise a set of processes to guarantee high data quality and better data management. In this paper, data quality mainly refers in a data storage sense (e.g. accuracy, completeness and integrity and not in a toxicological sense (e.g. the quality of experimental results. Results This paper reviews seven widely used predictive toxicology data sources and applications, with a particular focus on their data governance aspects, including: data accuracy, data completeness, data integrity, metadata and its management, data availability and data authorisation. This review reveals the current problems (e.g. lack of systematic and standard measures of data quality and desirable needs (e.g. better management and further use of captured metadata and the development of flexible multi-level user access authorisation schemas of predictive toxicology data sources development. The analytical results will help to address a significant gap in toxicology data quality assessment and lead to the development of novel frameworks for predictive toxicology data and model governance. Conclusions While the discussed public data sources are well developed, there nevertheless remain some gaps in the development of a data governance framework to support predictive toxicology. In this paper

  14. Generation and characterization of gasoline engine exhaust inhalation exposure atmospheres.

    Science.gov (United States)

    McDonald, Jacob D; Barr, Edward B; White, Richard K; Kracko, Dean; Chow, Judith C; Zielinska, Barbara; Grosjean, Eric

    2008-10-01

    Exposure atmospheres for a rodent inhalation toxicology study were generated from the exhaust of a 4.3-L gasoline engine coupled to a dynamometer and operated on an adapted California Unified Driving Cycle. Exposure levels were maintained at three different dilution rates. One chamber at the lowest dilution had particles removed by filtration. Each exposure atmosphere was characterized for particle mass, particle number, particle size distribution, and detailed chemical speciation. The majority of the mass in the exposure atmospheres was gaseous carbon monoxide, nitrogen oxides, and volatile organics, with small amounts of particle-bound carbon/ions and metals. The atmospheres varied according to the cycle, with the largest spikes in volatile organic and inorganic species shown during the "cold start" portion of the cycle. Ammonia present from the exhaust and rodents interacted with the gasoline exhaust to form secondary inorganic particles, and an increase in exhaust resulted in higher proportions of secondary inorganics as a portion of the total particle mass. Particle size had a median of 10-20 nm by number and approximately 150 nm by mass. Volatile organics matched the composition of the fuel, with large proportions of aliphatic and aromatic hydrocarbons coupled to low amounts of oxygenated organics. A new measurement technique revealed organics reacting with nitrogen oxides have likely resulted in measurement bias in previous studies of combustion emissions. Identified and measured particle organic species accounted for about 10% of total organic particle mass and were mostly aliphatic acids and polycyclic aromatic hydrocarbons.

  15. Precision toxicology based on single cell sequencing: an evolving trend in toxicological evaluations and mechanism exploration.

    Science.gov (United States)

    Zhang, Boyang; Huang, Kunlun; Zhu, Liye; Luo, Yunbo; Xu, Wentao

    2017-07-01

    In this review, we introduce a new concept, precision toxicology: the mode of action of chemical- or drug-induced toxicity can be sensitively and specifically investigated by isolating a small group of cells or even a single cell with typical phenotype of interest followed by a single cell sequencing-based analysis. Precision toxicology can contribute to the better detection of subtle intracellular changes in response to exogenous substrates, and thus help researchers find solutions to control or relieve the toxicological effects that are serious threats to human health. We give examples for single cell isolation and recommend laser capture microdissection for in vivo studies and flow cytometric sorting for in vitro studies. In addition, we introduce the procedures for single cell sequencing and describe the expected application of these techniques to toxicological evaluations and mechanism exploration, which we believe will become a trend in toxicology.

  16. Systems Toxicology: Real World Applications and Opportunities

    Science.gov (United States)

    2017-01-01

    Systems Toxicology aims to change the basis of how adverse biological effects of xenobiotics are characterized from empirical end points to describing modes of action as adverse outcome pathways and perturbed networks. Toward this aim, Systems Toxicology entails the integration of in vitro and in vivo toxicity data with computational modeling. This evolving approach depends critically on data reliability and relevance, which in turn depends on the quality of experimental models and bioanalysis techniques used to generate toxicological data. Systems Toxicology involves the use of large-scale data streams (“big data”), such as those derived from omics measurements that require computational means for obtaining informative results. Thus, integrative analysis of multiple molecular measurements, particularly acquired by omics strategies, is a key approach in Systems Toxicology. In recent years, there have been significant advances centered on in vitro test systems and bioanalytical strategies, yet a frontier challenge concerns linking observed network perturbations to phenotypes, which will require understanding pathways and networks that give rise to adverse responses. This summary perspective from a 2016 Systems Toxicology meeting, an international conference held in the Alps of Switzerland, describes the limitations and opportunities of selected emerging applications in this rapidly advancing field. Systems Toxicology aims to change the basis of how adverse biological effects of xenobiotics are characterized, from empirical end points to pathways of toxicity. This requires the integration of in vitro and in vivo data with computational modeling. Test systems and bioanalytical technologies have made significant advances, but ensuring data reliability and relevance is an ongoing concern. The major challenge facing the new pathway approach is determining how to link observed network perturbations to phenotypic toxicity. PMID:28362102

  17. Non-precautionary aspects of toxicology

    International Nuclear Information System (INIS)

    Grandjean, Philippe

    2005-01-01

    Empirical studies in toxicology aim at deciphering complex causal relationships, especially in regard to human disease etiologies. Several scientific traditions limit the usefulness of documentation from current toxicological research, in regard to decision-making based on the precautionary principle. Among non-precautionary aspects of toxicology are the focus on simplified model systems and the effects of single hazards, one by one. Thus, less attention is paid to sources of variability and uncertainty, including individual susceptibility, impacts of mixed and variable exposures, susceptible life-stages, and vulnerable communities. In emphasizing the need for confirmatory evidence, toxicology tends to penalize false positives more than false negatives. An important source of uncertainty is measurement error that results in misclassification, especially in regard to exposure assessment. Standard statistical analysis assumes that the exposure is measured without error, and imprecisions will usually result in an underestimation of the dose-effect relationship. In testing whether an effect could be considered a possible result of natural variability, a 5% limit for 'statistical significance' is usually applied, even though it may rule out many findings of causal associations, simply because the study was too small (and thus lacked statistical power) or because some imprecision or limited sensitivity of the parameters precluded a more definitive observation. These limitations may be aggravated when toxicology is influenced by vested interests. Because current toxicology overlooks the important goal of achieving a better characterization of uncertainties and their implications, research approaches should be revised and strengthened to counteract the innate ideological biases, thereby supporting our confidence in using toxicology as a main source of documentation and in using the precautionary principle as a decision procedure in the public policy arena

  18. Systems Toxicology: Real World Applications and Opportunities.

    Science.gov (United States)

    Hartung, Thomas; FitzGerald, Rex E; Jennings, Paul; Mirams, Gary R; Peitsch, Manuel C; Rostami-Hodjegan, Amin; Shah, Imran; Wilks, Martin F; Sturla, Shana J

    2017-04-17

    Systems Toxicology aims to change the basis of how adverse biological effects of xenobiotics are characterized from empirical end points to describing modes of action as adverse outcome pathways and perturbed networks. Toward this aim, Systems Toxicology entails the integration of in vitro and in vivo toxicity data with computational modeling. This evolving approach depends critically on data reliability and relevance, which in turn depends on the quality of experimental models and bioanalysis techniques used to generate toxicological data. Systems Toxicology involves the use of large-scale data streams ("big data"), such as those derived from omics measurements that require computational means for obtaining informative results. Thus, integrative analysis of multiple molecular measurements, particularly acquired by omics strategies, is a key approach in Systems Toxicology. In recent years, there have been significant advances centered on in vitro test systems and bioanalytical strategies, yet a frontier challenge concerns linking observed network perturbations to phenotypes, which will require understanding pathways and networks that give rise to adverse responses. This summary perspective from a 2016 Systems Toxicology meeting, an international conference held in the Alps of Switzerland, describes the limitations and opportunities of selected emerging applications in this rapidly advancing field. Systems Toxicology aims to change the basis of how adverse biological effects of xenobiotics are characterized, from empirical end points to pathways of toxicity. This requires the integration of in vitro and in vivo data with computational modeling. Test systems and bioanalytical technologies have made significant advances, but ensuring data reliability and relevance is an ongoing concern. The major challenge facing the new pathway approach is determining how to link observed network perturbations to phenotypic toxicity.

  19. Subchronic and chronic PCP treatment produces temporally distinct deficits in attentional set shifting and prepulse inhibition in rats.

    Science.gov (United States)

    Egerton, Alice; Reid, Lee; McGregor, Sandie; Cochran, Susan M; Morris, Brian J; Pratt, Judith A

    2008-05-01

    We have previously demonstrated that subchronic (five daily administrations of 2.6 mg/kg PCP) and chronic intermittent administration of 2.6 mg/kg PCP to rats produces hypofrontality and other neurochemical changes akin to schizophrenia pathology (Cochran et al., Neuropsychopharmacology, 28:265-275, 2003). We sought to determine whether behavioral alterations related to discrete aspects of schizophrenia are also induced by these PCP treatment regimes. Following administration of vehicle or PCP according to the protocols described above, rats were assessed for attentional set shifting ability, prepulse inhibition (PPI), or social interaction and the locomotor response to a challenge dose of amphetamine. Ability to shift attentional set was impaired 72 h after the last PCP administration following the subchronic and chronic intermittent treatment regimes. PPI was disrupted after each acute administration of PCP in animals under the subchronic treatment regime. However, PPI deficits were not sustained 72 h after the last of five daily administrations. In subchronic and chronic PCP treated animals, no change was found in social interaction behavior, and there was little change in baseline or amphetamine-stimulated locomotor activity, employed as an indicator of dopaminergic hyperfunction. The temporally distinct behavioral effects of these PCP treatment regimes suggest that PPI deficits relate directly to acute NMDA receptor antagonism, whereas the more enduring set shifting deficits relate to the longer term consequences of NMDA receptor blockade. Therefore, these subchronic and chronic PCP treatment regimes produce hypofrontality (Cochran et al., Neuropsychopharmacology, 28:265-275, 2003) and associated prefrontal cortex-dependent deficits in behavioral flexibility which mirror core deficits in schizophrenia.

  20. Inhaled actinides: some safety issues and some research problems

    International Nuclear Information System (INIS)

    Bair, W.J.

    1978-01-01

    The following topics are discussed: limited research funds; risk coefficients for inhaled particles; the hot particle hypothesis; the Gofman-Martell contention; critical tissues for inhaled actinides inhalation hazards associated with future nuclear fuel cycles; and approach to be used by the inhalation panel

  1. A study of the comparison between human and animal excretion data following inhalation exposure to plutonium 238 oxide aerosols

    International Nuclear Information System (INIS)

    Moss, W.D.; Martinez, G.; Gautier, M.A.

    1985-01-01

    Bioassay urine samples obtained since 1971 from eight Los Alamos employees, accidentally exposed by inhalation to high-fired plutonium-238 oxide aerosols, were studied and compared with excretion data obtained from Beagle dogs exposed to /sup 238/PuO/sub 2/ aerosols. The early period Pu human excretion data from the inhalation exposure were unexpected and were unlike previously studied occupational exposure urinary data obtained at Los Alamos. The initial urine samples collected on day one were below the detection limits of the analytical method (0.01 pCi). Within thirty days, however, detectible concentrations of Pu were measured in the urine for several of the exposed personnel. The amounts of Pu excreted continued to increase in each of the cases throughout the first year and the individual patterns of Pu excretion were similar. The human urinary excretion data was compared with similar excretion data obtained from an animal study conducted by the Inhalation Toxicology Research Institute (Me81). In the animal study, Beagle dogs received inhalation exposure to one of three sizes of monodisperse of polydisperse aerosol of /sup 238/PuO/sub 2/. Periodic sacrifice of pairs of dogs during the 4 years after the inhalation exposure provided data on the retention, translocation and mode of excretion of /sup 238/Pu. The comparison of human and animal /sup 238/Pu excretion data supported the observation that the excretion data were similar between the two species and that the animal excretion models can be applied to predict the human /sup 238/Pu excretion following inhalation exposure to high-fired oxides of /sup 238/Pu

  2. Toxicological study of a polyphenyl-type chemical compound used by the thermal transfer department; Etude toxicologique d'un produit chimique du type polyphenyle utilise par la section des transferts thermiques

    Energy Technology Data Exchange (ETDEWEB)

    Rinaldi, R.; Alix, D.

    1961-07-01

    This note reports an experimentation of toxicological tests performed on two mice breed by different ways (skin absorption, respiratory route, digestive tract) in order to assess the toxicology of a chemical compound containing a bi-phenyl eutectic and bi-phenyl oxide. The authors describe effects noticed among mice depending on the absorption way. They notice the caustic action of the product, but that an accidental absorption through the digestive tract would not result in an acute and severe intoxication. As far as chronic intoxication is concerned, daily inhalations do not seem to have any haematological impact on mice.

  3. Know How to Use Your Asthma Inhaler

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    Full Text Available ... Evaluation Roadblocks 1A. Focus On: Walking Through the Steps and Standards 2. Getting Started 3. Describing and ... to use your metered dose inhaler. Print the step-by-step instructions and keep them with your ...

  4. Know How to Use Your Asthma Inhaler

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    Full Text Available ... on this page will be unavailable. For more information about this message, please visit this page: About CDC.gov . ... Asthma Action Plan Flu Shots Inhalers Data, Statistics, ...

  5. Know How to Use Your Asthma Inhaler

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    Full Text Available ... Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers Data, Statistics, and Surveillance Most ... control over their asthma. Quick Links Asthma Action Plan America Breathing Easier [PDF – 1.1 MB] ASL ...

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    Full Text Available ... Brochures Facts Guidance on Spirometry Parents Preventing and Controlling Tools for Control Triggers Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers Data, Statistics, ...

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    Full Text Available ... How to Use Your Asthma Inhaler Recommend on Facebook Tweet Share Compartir You can control your asthma ... RSS ABOUT About CDC Jobs Funding LEGAL Policies Privacy FOIA No Fear Act OIG 1600 Clifton Road ...

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    Full Text Available ... Inhaler Recommend on Facebook Tweet Share Compartir You can control your asthma and avoid an attack by ... you to do and by avoiding things that can cause an attack. Watch a video to follow ...

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    Full Text Available ... Controlling Tools for Control Triggers Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers ... Case Studies Open Airways for Schools Asthma Care Training Wee Wheezers Adventures of Puff Inner City Asthma ...

  10. Know How to Use Your Asthma Inhaler

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    Full Text Available ... Controlling Tools for Control Triggers Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers ... YouTube Instagram Listen Watch RSS ABOUT About CDC Jobs Funding LEGAL Policies Privacy FOIA No Fear Act ...

  11. Know How to Use Your Asthma Inhaler

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    Full Text Available ... In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers Data, Statistics, and Surveillance Most Recent ... AsthmaStats Asthma as the Underlying Cause of Death Flu Vaccination among Adults with Current Asthma Flu Vaccination ...

  12. Health risks associated with inhaled nasal toxicants

    NARCIS (Netherlands)

    Feron, VJ; Arts, JHE; Kuper, CF; Slootweg, PJ; Woutersen, RA

    2001-01-01

    Health risks of inhaled nasal toxicants were reviewed with emphasis on chemically induced nasal lesions in humans, sensory irritation, olfactory and trigeminal nerve toxicity, nasal immunopathology and carcinogenesis, nasal responses to chemical mixtures, in vitro models, and nasal dosimetry- and

  13. Know How to Use Your Asthma Inhaler

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    Full Text Available ... for Control Triggers Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers Data, Statistics, ... Mixed Methods 5. Purpose Informs Design Other Evaluation Resources Multimedia ... USA.gov TOP

  14. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... Asthma & Community Health Know How to Use Your Asthma Inhaler Recommend on Facebook Tweet Share Compartir You can control your asthma and avoid an attack by taking your medicine ...

  15. Know How to Use Your Asthma Inhaler

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    Full Text Available ... and Publications Related Articles, Publications, and Links Asthma’s Impact on the Nation Fact Sheet State Data Profiles ( ... How to Use Your Asthma Inhaler Recommend on Facebook Tweet Share Compartir You can control your asthma ...

  16. [INHALED ANTIBIOTICS IN TREATMENT OF NOSOCOMIAL PNEUMONIA].

    Science.gov (United States)

    Kuzovlev, A N; Moroz, V V; Golubev, A M

    2015-01-01

    Nosocomial pneumonia is the most common infection in intensive care units. Currently the problem of resistance of noso-comial pathogens to miost of antibiotics is crucial. Using of inhaled antibiotics in combination with intravenous drugs is eff ective and safe method for treatment of nosocomial pneumonia. The literature review describes current opportunities of ihhaled antibiotic therapy of nosocomial pneumonia, descriptions of drugs, the advantages and disadvantages of this treatment. Special attention is paid for using inhaled aminoglycosides for nosocomial pneumonia.

  17. Lung Deposition Analyses of Inhaled Toxic Aerosols in Conventional and Less Harmful Cigarette Smoke: A Review

    Directory of Open Access Journals (Sweden)

    Yu Feng

    2013-09-01

    Full Text Available Inhaled toxic aerosols of conventional cigarette smoke may impact not only the health of smokers, but also those exposed to second-stream smoke, especially children. Thus, less harmful cigarettes (LHCs, also called potential reduced exposure products (PREPs, or modified risk tobacco products (MRTP have been designed by tobacco manufacturers to focus on the reduction of the concentration of carcinogenic components and toxicants in tobacco. However, some studies have pointed out that the new cigarette products may be actually more harmful than the conventional ones due to variations in puffing or post-puffing behavior, different physical and chemical characteristics of inhaled toxic aerosols, and longer exposure conditions. In order to understand the toxicological impact of tobacco smoke, it is essential for scientists, engineers and manufacturers to develop experiments, clinical investigations, and predictive numerical models for tracking the intake and deposition of toxicants of both LHCs and conventional cigarettes. Furthermore, to link inhaled toxicants to lung and other diseases, it is necessary to determine the physical mechanisms and parameters that have significant impacts on droplet/vapor transport and deposition. Complex mechanisms include droplet coagulation, hygroscopic growth, condensation and evaporation, vapor formation and changes in composition. Of interest are also different puffing behavior, smoke inlet conditions, subject geometries, and mass transfer of deposited material into systemic regions. This review article is intended to serve as an overview of contributions mainly published between 2009 and 2013, focusing on the potential health risks of toxicants in cigarette smoke, progress made in different approaches of impact analyses for inhaled toxic aerosols, as well as challenges and future directions.

  18. Depletion of liver glutathione levels in rats: a potential confound of nose-only inhalation.

    Science.gov (United States)

    Fechter, Laurence D; Nelson-Miller, Alisa; Gearhart, Caroline

    2008-07-01

    Nose-only inhalation exposure chambers offer key advantages to whole-body systems, particularly when aerosol or mixed aerosol-vapor exposures are used. Specifically, nose-only chambers provide enhanced control over the route of exposure and dose by minimizing the deposition of particles either on the subjects skin/fur or on surfaces of a whole-body exposure system. In the current series of experiments, liver, brain, and lung total glutathione (GSH) levels were assessed following either nose-only or whole-body exposures to either jet fuel or to clean, filtered air. The data were compared to untreated control subjects. Acute nose-only inhalation exposures of rats resulted in a significant depletion of liver GSH levels both in subjects that were exposed to clean, filtered air as well as those exposed to JP-8 jet fuel and to a synthetic jet fuel. Glutathione levels were not altered in lung or brain tissue. Whole-body inhalation exposure had no effect on GSH levels in any tissue for any of the treatment groups. A second experiment demonstrated that the loss of GSH did not occur if rats were anaesthetized prior to and during nose-only exposure to clean, filtered air or to mixed hydrocarbons. These data appear to be consistent with studies demonstrating depletion in liver GSH levels among rats subjected to restraint stress. Finally, the depletion of GSH that was observed in liver following a single acute exposure was reduced following five daily exposures to clean, filtered air, suggesting the possibility of habituation to restraint in the nose-only exposure chamber. The finding that placement in a nose-only exposure chamber per se yields liver GSH depletion raises the possibility of an interaction between this mode of toxicant exposure and the toxicological effects of certain inhaled test substances.

  19. Forensic medical evaluation of deaths resulting from inhalation of cigarette lighter refill fuel in Turkey.

    Science.gov (United States)

    Özdemir, Erdinç; Eş, Hüseyin; Demir, Muhammet; Üzün, İbrahim

    2017-01-01

    Voluntary inhalation/abuse of volatile substances is an important public health problem which especially affects adolescent and young populations worldwide and may be encountered in all socioeconomic and cultural levels. Lighter gas abuse-related death is still an important health problem in Turkey. In this study, 25,265 case files and final reports submitted to the Institute of Forensic Medicine of the First Specialization Board between January 2011 and December 2015 were evaluated retrospectively. In 56 of these cases, lighter gas inhalation (n-butane, propane, isobutane) was recorded as the cause of death. All subjects were male with a mean age of 16.8years. According to eyewitness and crime scene investigation reports, in 48 (85.7%) of the cases, a lighter refill container was found at the scene. It was determined that 21.4% of the cases used a plastic bag to increase the effects of lighter gas and 76.8% inhaled the lighter gas via their mouth and nose. The toxicological analysis of the samples taken while hospitalized showed no lighter refill components (n-butane, propane, isobutane) in 66% of the cases, n-butane in 32.1% of the cases, and n-butane+propane+isobutane in 1.9% of the cases. The importance of lighter gas inhalation-related deaths in Turkey has been increasing. Strict measures against the abuse of these very dangerous substances should be undertaken by the mutual efforts of medical specialists and legislators. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. ACToR - Aggregated Computational Toxicology Resource

    International Nuclear Information System (INIS)

    Judson, Richard; Richard, Ann; Dix, David; Houck, Keith; Elloumi, Fathi; Martin, Matthew; Cathey, Tommy; Transue, Thomas R.; Spencer, Richard; Wolf, Maritja

    2008-01-01

    ACToR (Aggregated Computational Toxicology Resource) is a database and set of software applications that bring into one central location many types and sources of data on environmental chemicals. Currently, the ACToR chemical database contains information on chemical structure, in vitro bioassays and in vivo toxicology assays derived from more than 150 sources including the U.S. Environmental Protection Agency (EPA), Centers for Disease Control (CDC), U.S. Food and Drug Administration (FDA), National Institutes of Health (NIH), state agencies, corresponding government agencies in Canada, Europe and Japan, universities, the World Health Organization (WHO) and non-governmental organizations (NGOs). At the EPA National Center for Computational Toxicology, ACToR helps manage large data sets being used in a high-throughput environmental chemical screening and prioritization program called ToxCast TM

  1. Toxicology research projects directory, 1978. Monthly repts

    International Nuclear Information System (INIS)

    1978-01-01

    The Toxicology Research Projects Directory is a monthly publication of ongoing research projects in toxicology and related fields selected from the files of the Smithsonian Science Information Exchange (SSIE). Each issue lists toxicology-related research projects reported to SSIE during the one-month period preceding that issue. Each of the summaries is categorized by scientific discipline and assigned a unique identification number for cross-referencing from the Directory Indexes--Subject, Investigator, Performing Organization, Supporting Agency, and Master Grant Number. The thirteenth issue consists of Cumulative Indexes for the entire volume with referencing to projects in all of the previous twelve issues. The emphasis of the Directory is on the manifestations of the exposure of man and animals to toxic substances. Projects are classified by toxic agents, research orientation, and areas of environmental concern

  2. Prospects for applying synthetic biology to toxicology

    DEFF Research Database (Denmark)

    Behrendorff, James Bruce Yarnton H; Gillam, Elizabeth M.J.

    2017-01-01

    The 30 years since the inception of Chemical Research in Toxicology, game-changing advances in chemical and molecular biology, the fundamental disciplines underpinning molecular toxicology, have been made. While these have led to important advances in the study of mechanisms by which chemicals...... damage cells and systems, there has been less focus on applying these advances to prediction, detection, and mitigation of toxicity. Over the last ∼15 years, synthetic biology, the repurposing of biological "parts" in systems engineered for useful ends, has been explored in other areas of the biomedical...... and life sciences, for such applications as detecting metabolites, drug discovery and delivery, investigating disease mechanisms, improving medical treatment, and producing useful chemicals. These examples provide models for the application of synthetic biology to toxicology, which, for the most part, has...

  3. Comparison of toxicological and radiological aspects of K basins sludge

    International Nuclear Information System (INIS)

    RITTMANN, P.D.

    1999-01-01

    The composition of various K Basins sludge is evaluated for its toxicological and radiological impacts downwind from accidents. It is shown that the radiological risk evaluation guidelines are always more limiting than the toxicological risk evaluation guidelines

  4. Intestinal circulation during inhalation anesthesia

    International Nuclear Information System (INIS)

    Tverskoy, M.; Gelman, S.; Fowler, K.C.; Bradley, E.L.

    1985-01-01

    This study was designed to evaluate the influence of inhalational agents on the intestinal circulation in an isolated loop preparation. Sixty dogs were studied, using three intestinal segments from each dog. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mmHg. A mixture of 86 Rb and 9-microns spheres labeled with 141 Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A very strong and significant correlation was found between rubidium clearance and microsphere entrapment (r = 0.97, P less than 0.0001). Nitrous oxide anesthesia was accompanied by a higher vascular resistance (VR), lower flow (F), rubidium clearance (Cl-Rb), and microspheres entrapment (Cl-Sph) than pentobarbital anesthesia, indicating that the vascular bed in the intestinal segment was constricted and flow (total and nutritive) decreased. Halothane, enflurane, and isoflurane anesthesia were accompanied by a much lower arteriovenous oxygen content difference (AVDO 2 ) and oxygen uptake than pentobarbital or nitrous oxide. Compared with pentobarbital, enflurane anesthesia was not accompanied by marked differences in VR, F, Cl-Rb, and Cl-Sph; halothane at 2 MAC decreased VR and increased F and Cl-Rb while isoflurane increased VR and decreased F. alpha-Adrenoceptor blockade with phentolamine (1 mg . kg-1) abolished isoflurane-induced vasoconstriction, suggesting that the increase in VR was mediated via circulating catecholamines

  5. Toxicologic Assessment of a Commercial Decolorized Whole Leaf Aloe Vera Juice, Lily of the Desert Filtered Whole Leaf Juice with Aloesorb

    Science.gov (United States)

    Winters, Wallace D.; Scott, Michael; David, Andrew; Gillis, Glenn; Stoufflet, Thaya; Nair, Anand; Kousoulas, Konstantine

    2013-01-01

    Aloe vera, a common ingredient in cosmetics, is increasingly being consumed as a beverage supplement. Although consumer interest in aloe likely stems from its association with several health benefits, a concern has also been raised by a National Toxicology Program Report that a nondecolorized whole leaf aloe vera extract taken internally by rats was associated with intestinal mucosal hyperplasia and ultimately malignancy. We tested a decolorized whole leaf (DCWL) aloe vera, treated with activated charcoal to remove the latex portion of the plant, for genotoxicity in bacteria, acute/subacute toxicity in B6C3F1 mice, and subchronic toxicity in F344 rats. We found this DCWL aloe vera juice to be nongenotoxic in histidine reversion and DNA repair assays. Following acute administration, mice exhibited no adverse signs at 3- or 14-day evaluation periods. When fed to male and female F344 rats over 13 weeks, DCWL aloe led to no toxicity as assessed by behavior, stools, weight gain, feed consumption, organ weights, and hematologic or clinical chemistry profiles. These rats had intestinal mucosal morphologies—examined grossly and microscopically—that were similar to controls. Our studies show that oral administration of this DCWL aloe juice has a different toxicology profile than that of the untreated aloe juice at exposures up to 13 weeks. PMID:23554812

  6. Toxicologic Assessment of a Commercial Decolorized Whole Leaf Aloe Vera Juice, Lily of the Desert Filtered Whole Leaf Juice with Aloesorb

    Directory of Open Access Journals (Sweden)

    Inder Sehgal

    2013-01-01

    Full Text Available Aloe vera, a common ingredient in cosmetics, is increasingly being consumed as a beverage supplement. Although consumer interest in aloe likely stems from its association with several health benefits, a concern has also been raised by a National Toxicology Program Report that a nondecolorized whole leaf aloe vera extract taken internally by rats was associated with intestinal mucosal hyperplasia and ultimately malignancy. We tested a decolorized whole leaf (DCWL aloe vera, treated with activated charcoal to remove the latex portion of the plant, for genotoxicity in bacteria, acute/subacute toxicity in B6C3F1 mice, and subchronic toxicity in F344 rats. We found this DCWL aloe vera juice to be nongenotoxic in histidine reversion and DNA repair assays. Following acute administration, mice exhibited no adverse signs at 3- or 14-day evaluation periods. When fed to male and female F344 rats over 13 weeks, DCWL aloe led to no toxicity as assessed by behavior, stools, weight gain, feed consumption, organ weights, and hematologic or clinical chemistry profiles. These rats had intestinal mucosal morphologies—examined grossly and microscopically—that were similar to controls. Our studies show that oral administration of this DCWL aloe juice has a different toxicology profile than that of the untreated aloe juice at exposures up to 13 weeks.

  7. Developmental toxicology: adequacy of current methods.

    Science.gov (United States)

    Peters, P W

    1998-01-01

    Toxicology embraces several disciplines such as carcinogenicity, mutagenicity and reproductive toxicity. Reproductive toxicology is concerned with possible effects of substances on the reproductive process, i.e. on sexual organs and their functions, endocrine regulation, fertilization, transport of the fertilized ovum, implantation, and embryonic, fetal and postnatal development, until the end-differentiation of the organs is achieved. Reproductive toxicology is divided into areas related to male and female fertility, and developmental toxicology. Developmental toxicology can be further broken down into prenatal and postnatal toxicology. Today, much new information is available about the origins of developmental disorders resulting from chemical exposure. While these findings seem to promise important new developments in methodology and research, there is a danger of losing sight of the precepts and principles established in the light of existing knowledge. There is also a danger that we may fail to correct shortcomings in our existing procedures and practice. The aim of this presentation is to emphasize the importance of testing substances for their impact in advance of their use and to underline that we must use the best existing tools for carrying out risk assessments. Moreover, it needs to be stressed that there are many substances that are never assessed with respect to reproductive and developmental toxicity. Similarly, our programmes for post-marketing surveillance with respect to developmental toxicology are grossly inadequate. Our ability to identify risks to normal development and reproduction would be much improved, first if a number of straightforward precepts were always followed and second, if we had a clearer understanding of what we mean by risk and acceptable levels of risk in the context of development. Other aims of this paper are: to stress the complexity of the different stages of normal prenatal development; to note the principles that are

  8. Toxicological benchmarks for wildlife: 1996 Revision

    International Nuclear Information System (INIS)

    Sample, B.E.; Opresko, D.M.; Suter, G.W., II.

    1996-06-01

    The purpose of this report is to present toxicological benchmarks for assessment of effects of certain chemicals on mammalian and avian wildlife species. Publication of this document meets a milestone for the Environmental Restoration (ER) Risk Assessment Program. This document provides the ER Program with toxicological benchmarks that may be used as comparative tools in screening assessments as well as lines of evidence to support or refute the presence of ecological effects in ecological risk assessments. The chemicals considered in this report are some that occur at US DOE waste sites, and the wildlife species evaluated herein were chosen because they represent a range of body sizes and diets

  9. IRIS Toxicological Review of Trichloroethylene (TCE) ...

    Science.gov (United States)

    EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of Trichloroethylene (TCE) that when finalized will appear on the Integrated Risk Information System (IRIS) database. The purpose of this Toxicological Review is to provide scientific support and rationale for the hazard and dose-response assessment in IRIS pertaining to chronic exposure to trichloroethylene. It is not intended to be a comprehensive treatise on the chemical or toxicological nature of trichloroethylene.

  10. [Forensic toxicology, a growing scientific discipline].

    Science.gov (United States)

    Augsburger, Marc; Staub, Christian

    2008-07-02

    Forensic toxicology has to bring evidence of substances that could have been involved directly or indirectly in the cause of death or that could influence the behaviour of somebody. The increase of the consumption of illegal and legal drugs in modern societies during last decades gave a boost to forensic toxicology. Moreover, improvement with analytical technology gave tools with high degrees of sensitivity and specificity for the screening and quantification of a large amount of substances in various biological specimens, even with very low concentration resulting of a single dose of medication.

  11. Toxicological benchmarks for wildlife: 1996 Revision

    Energy Technology Data Exchange (ETDEWEB)

    Sample, B.E.; Opresko, D.M.; Suter, G.W., II

    1996-06-01

    The purpose of this report is to present toxicological benchmarks for assessment of effects of certain chemicals on mammalian and avian wildlife species. Publication of this document meets a milestone for the Environmental Restoration (ER) Risk Assessment Program. This document provides the ER Program with toxicological benchmarks that may be used as comparative tools in screening assessments as well as lines of evidence to support or refute the presence of ecological effects in ecological risk assessments. The chemicals considered in this report are some that occur at US DOE waste sites, and the wildlife species evaluated herein were chosen because they represent a range of body sizes and diets.

  12. Crocin Restores Hypotensive Effect of Subchronic Administration of Diazinon in Rats

    Directory of Open Access Journals (Sweden)

    Marjan Razavi

    2013-01-01

    Full Text Available Objective(s: In this study, the effects of crocin against subchronic toxicity of diazinon (DZN on systolic blood pressure (SBP and heart rate (HR were evaluated in rats. Materials and Methods: Rats were equally divided into 7 groups; control (corn oil, DZN (15 mg/kg, crocin (each group received 12.5, 25 or 50 mg/kg crocin plus DZN, vitamin E (200 IU/kg plus DZN and crocin (50 mg/kg treated groups.  Rats were given DZN via gavage once a day for 4 weeks. Vitamin E (three times per week and crocin (once a day were intraperitoneally injected to rats for 4 weeks. Plasma cholinesterase activity (Elman method, malondealdehyde (MDA levels in the aortic tissue (Thiobarbituric acid reactive substances or TBARS method; SBP and HR (tail cuff method were evaluated at the end of 4th week. Results: A significant decrease in cholinesterase activity was observed in DZN group (P< 0.001. Crocin did not show any effects on cholinesterase activity. DZN increased MDA levels in aortic tissue (P< 0.001 in comparison with control group. Crocin and vitamin E plus DZN decreased MDA elevation induced by DZN in aortic tissue. DZN significantly reduced SBP (P< 0.01 and increased HR (P< 0.001 in comparison with control. Concurrent administration of crocin and DZN, improved the reduction of SBP and the elevation of HR induced by DZN in rat. Crocin alone did not have any effect on SBP and HR. Conclusion: This study showed that concurrent administration of crocin and DZN could restore the effects of subchronic DZN administration on SBP and HR in rats.

  13. Sub-chronic agmatine treatment modulates hippocampal neuroplasticity and cell survival signaling pathways in mice.

    Science.gov (United States)

    Freitas, Andiara E; Bettio, Luis E B; Neis, Vivian B; Moretti, Morgana; Ribeiro, Camille M; Lopes, Mark W; Leal, Rodrigo B; Rodrigues, Ana Lúcia S

    2014-11-01

    Agmatine is an endogenous neuromodulator which, based on animal and human studies, is a putative novel antidepressant drug. In this study, we investigated the ability of sub-chronic (21 days) p.o. agmatine administration to produce an antidepressant-like effect in the tail suspension test and examined the hippocampal cell signaling pathways implicated in such an effect. Agmatine at doses of 0.01 and 0.1 mg/kg (p.o.) produced a significant antidepressant-like effect in the tail suspension test and no effect in the open-field test. Additionally, agmatine (0.001-0.1 mg/kg, p.o.) increased the phosphorylation of protein kinase A substrates (237-258% of control), protein kinase B/Akt (Ser(473)) (116-127% of control), glycogen synthase kinase-3β (Ser(9)) (110-113% of control), extracellular signal-regulated kinases 1/2 (119-137% and 121-138% of control, respectively) and cAMP response elements (Ser(133)) (127-152% of control), and brain-derived-neurotrophic factor (137-175% of control) immunocontent in a dose-dependent manner in the hippocampus. Agmatine (0.001-0.1 mg/kg, p.o.) also reduced the c-jun N-terminal kinase 1/2 phosphorylation (77-71% and 65-51% of control, respectively). Neither protein kinase C nor p38(MAPK) phosphorylation was altered under any experimental conditions. Taken together, the present study extends the available data on the mechanisms that underlie the antidepressant action of agmatine by showing an antidepressant-like effect following sub-chronic administration. In addition, our results are the first to demonstrate the ability of agmatine to elicit the activation of cellular signaling pathways associated with neuroplasticity/cell survival and the inhibition of signaling pathways associated with cell death in the hippocampus. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Sub-chronic lead exposure produces β1-adrenoceptor downregulation decreasing arterial pressure reactivity in rats.

    Science.gov (United States)

    Toscano, Cindy Medici; Simões, Maylla Ronacher; Alonso, Maria Jesus; Salaices, Mercedes; Vassallo, Dalton Valentim; Fioresi, Mirian

    2017-07-01

    Lead is considered a causative factor for hypertension and other cardiovascular diseases. To investigate the effects of sub-chronic lead exposure on blood pressure reactivity and cardiac β 1 -adrenoceptor activity and to evaluate whether the effects found in vitro are similar to those found in vivo. Male Wistar rats were randomly distributed into two groups: control rats (Ct) and rats administered drinking water containing 100ppm lead (Pb) for 30days. Blood pressure in the Pb rats increased starting from the first week of treatment until the end of the study [systolic blood pressure, Ct: 122±4 vs. Pb: 143±3mmHg; diastolic blood pressure, Ct: 63±4 vs. Pb: 84±4mmHg]. The heart rate was also increased (Ct: 299±11 vs. Pb: 365±11bpm), but the pressure reactivity to phenylephrine was decreased. Losartan and hexamethonium exhibited a greater reduction in blood pressure of Pb rats than in the Ct rats. Isoproterenol increased the left ventricular systolic and end-diastolic pressure, and heart rate only in Ct rats, suggesting that lead induced β 1 -adrenoceptor downregulation. Indomethacin reduced the blood pressure and heart rate in the Pb rats, suggesting the involvement of cyclooxygenase-derived products (which are associated with reduced nitric oxide bioavailability) in this process. These findings offer further evidence that the effects of sub-chronic lead exposure in vitro can be reproduced in vivo-even at low concentrations-thus triggering mechanisms for the development of hypertension. Therefore, lead should be considered an environmental risk factor for cardiovascular disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Toxicological assessment of the hydroethanolic leaf extract of ...

    African Journals Online (AJOL)

    Introduction: Clerodendrum capitatum (Willd) Schumach. & Thonn (Lamiaceae) is used in African traditional medicine for the treatment of malaria, hypertension, obesity, jaundice and diabetes however there is lack of experimental data on its possible toxicity. This study investigated the acute and 28 days sub-chronic toxicity ...

  16. 40 CFR 161.340 - Toxicology data requirements.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Toxicology data requirements. 161.340... Toxicology data requirements. (a) Table. Sections 161.100 through 161.102 describe how to use this table to determine the toxicology data requirements and the substance to be tested. Kind of data required (b) Notes...

  17. Assessing inhalation injury in the emergency room

    Directory of Open Access Journals (Sweden)

    Tanizaki S

    2015-07-01

    Full Text Available Shinsuke Tanizaki Department of Emergency Medicine, Fukui Prefectural Hospital, Fukui, Japan Abstract: Respiratory tract injuries caused by inhalation of smoke or chemical products are related to significant morbidity and mortality. While many strategies have been built up to manage cutaneous burn injuries, few logical diagnostic strategies for patients with inhalation injuries exist and almost all treatment is supportive. The goals of initial management are to ensure that the airway allows adequate oxygenation and ventilation and to avoid ventilator-induced lung injury and substances that may complicate subsequent care. Intubation should be considered if any of the following signs exist: respiratory distress, stridor, hypoventilation, use of accessory respiratory muscles, blistering or edema of the oropharynx, or deep burns to the face or neck. Any patients suspected to have inhalation injuries should receive a high concentration of supplemental oxygen to quickly reverse hypoxia and to displace carbon monoxide from protein binding sites. Management of carbon monoxide and cyanide exposure in smoke inhalation patients remains controversial. Absolute indications for hyperbaric oxygen therapy do not exist because there is a low correlation between carboxyhemoglobin levels and the severity of the clinical state. A cyanide antidote should be administered when cyanide poisoning is clinically suspected. Although an ideal approach for respiratory support of patients with inhalation injuries do not exist, it is important that they are supported using techniques that do not further exacerbate respiratory failure. A well-organized strategy for patients with inhalation injury is critical to reduce morbidity and mortality. Keywords: inhalation injury, burn, carbon monoxide poisoning, cyanide poisoning

  18. Systems toxicology: applications of toxicogenomics, transcriptomics, proteomics and metabolomics in toxicology

    NARCIS (Netherlands)

    Heijne, W.H.M.; Kienhuis, A.S.; Ommen, van B.; Stierum, R.; Groten, J.P.

    2005-01-01

    Toxicogenomics can facilitate the identification and characterization of toxicity, as illustrated in this review. Toxicogenomics, the application of the functional genomics technologies (transcriptomics, proteomics and metabolomics) in toxicology enables the study of adverse effects of xenobiotic

  19. Inhaled mannitol for cystic fibrosis.

    Science.gov (United States)

    Nevitt, Sarah J; Thornton, Judith; Murray, Clare S; Dwyer, Tiffany

    2018-02-09

    Several agents are used to clear secretions from the airways of people with cystic fibrosis. Mannitol increases mucociliary clearance, but its exact mechanism of action is unknown. The dry powder formulation of mannitol may be more convenient and easier to use compared with established agents which require delivery via a nebuliser. Phase III trials of inhaled dry powder mannitol for the treatment of cystic fibrosis have been completed and it is now available in Australia and some countries in Europe. This is an update of a previous review. To assess whether inhaled dry powder mannitol is well tolerated, whether it improves the quality of life and respiratory function in people with cystic fibrosis and which adverse events are associated with the treatment. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic databases, handsearching relevant journals and abstracts from conferences.Date of last search: 28 September 2017. All randomised controlled studies comparing mannitol with placebo, active inhaled comparators (for example, hypertonic saline or dornase alfa) or with no treatment. Authors independently assessed studies for inclusion, carried out data extraction and assessed the risk of bias in included studies. The quality of the evidence was assessed using GRADE. Six studies (reported in 50 publications) were included with a total of 784 participants.Duration of treatment in the included studies ranged from 12 days to six months, with open-label treatment for an additional six months in two of the studies. Five studies compared mannitol with control (a very low dose of mannitol or non-respirable mannitol) and the final study compared mannitol to dornase alfa alone and to mannitol plus dornase alfa. Two large studies had a similar parallel design and provided data for 600 participants, which could be pooled where data for a particular outcome and time point were

  20. Toxicological aspects of fuel and exhaust gas

    International Nuclear Information System (INIS)

    Avella, F.

    1993-01-01

    Some aspects concerning fuels (gasoline) and gas exhaust vehicle emissions toxicology are briefly examined in light of the results reported in recent literature on this argument. Many experimental studies carried out on animals and men turn out incomplete and do not allow thorough evaluations, for every aspect, of the risk to which men and the environment are subjected

  1. Evolution of Computational Toxicology-from Primitive ...

    Science.gov (United States)

    Presentation at the Health Canada seminar in Ottawa, ON, Canada on Nov. 15. 2016 Presentation at the Health Canada seminar in Ottawa, ON, Canada on Nov. 15. 2016 on the Evolution of Computational Toxicology-from Primitive Beginnings to Sophisticated Application

  2. Good cell culture practices &in vitro toxicology.

    Science.gov (United States)

    Eskes, Chantra; Boström, Ann-Charlotte; Bowe, Gerhard; Coecke, Sandra; Hartung, Thomas; Hendriks, Giel; Pamies, David; Piton, Alain; Rovida, Costanza

    2017-12-01

    Good Cell Culture Practices (GCCP) is of high relevance to in vitro toxicology. The European Society of Toxicology In Vitro (ESTIV), the Center for Alternatives for Animal Testing (CAAT) and the In Vitro Toxicology Industrial Platform (IVTIP) joined forces to address by means of an ESTIV 2016 pre-congress session the different aspects and applications of GCCP. The covered aspects comprised the current status of the OECD guidance document on Good In Vitro Method Practices, the importance of quality assurance for new technological advances in in vitro toxicology including stem cells, and the optimized implementation of Good Manufacturing Practices and Good Laboratory Practices for regulatory testing purposes. General discussions raised the duality related to the difficulties in implementing GCCP in an academic innovative research framework on one hand, and on the other hand, the need for such GCCP principles in order to ensure reproducibility and robustness of in vitro test methods for toxicity testing. Indeed, if good cell culture principles are critical to take into consideration for all uses of in vitro test methods for toxicity testing, the level of application of such principles may depend on the stage of development of the test method as well as on the applications of the test methods, i.e., academic innovative research vs. regulatory standardized test method. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Research Models in Developmental Behavioral Toxicology.

    Science.gov (United States)

    Dietrich, Kim N.; Pearson, Douglas T.

    Developmental models currently used by child behavioral toxicologists and teratologists are inadequate to address current issues in these fields. Both child behavioral teratology and toxicology scientifically study the impact of exposure to toxic agents on behavior development: teratology focuses on prenatal exposure and postnatal behavior…

  4. A medical-toxicological view of tattooing

    DEFF Research Database (Denmark)

    Laux, Peter; Tralau, Tewes; Tentschert, Jutta

    2016-01-01

    of infections. Meanwhile, the increasing popularity of tattooing has led to the development of many new colours, allowing tattoos to be more spectacular than ever before. However, little is known about the toxicological risks of the ingredients used. For risk assessment, safe intradermal application...

  5. Toxicodynetics: A new discipline in clinical toxicology.

    Science.gov (United States)

    Baud, F J; Houzé, P; Villa, A; Borron, S W; Carli, P

    2016-05-01

    Regarding the different disciplines that encompass the pharmacology and the toxicology, none is specifically dedicated to the description and analysis of the time-course of relevant toxic effects both in experimental and clinical studies. The lack of a discipline devoted to this major field in toxicology results in misconception and even in errors by clinicians. Review of the basic different disciplines that encompass pharmacology toxicology and comparing with the description of the time-course of effects in conditions in which toxicological analysis was not performed or with limited analytical evidence. Review of the literature clearly shows how misleading is the current extrapolation of toxicokinetic data to the description of the time-course of toxic effects. A new discipline entitled toxicodynetics should be developed aiming at a more systematic description of the time-course of effects in acute human and experimental poisonings. Toxicodynetics might help emergency physicians in risk assessment when facing a poisoning and contribute to a better assessment of quality control of data collected by poison control centres. Toxicodynetics would also allow a quantitative approach to the clinical effects resulting from drug-drug interaction. Copyright © 2016. Published by Elsevier Masson SAS.

  6. Metabolomics in Toxicology and Preclinical Research

    Science.gov (United States)

    Ramirez, Tzutzuy; Daneshian, Mardas; Kamp, Hennicke; Bois, Frederic Y.; Clench, Malcolm R.; Coen, Muireann; Donley, Beth; Fischer, Steven M.; Ekman, Drew R.; Fabian, Eric; Guillou, Claude; Heuer, Joachim; Hogberg, Helena T.; Jungnickel, Harald; Keun, Hector C.; Krennrich, Gerhard; Krupp, Eckart; Luch, Andreas; Noor, Fozia; Peter, Erik; Riefke, Bjoern; Seymour, Mark; Skinner, Nigel; Smirnova, Lena; Verheij, Elwin; Wagner, Silvia; Hartung, Thomas; van Ravenzwaay, Bennard; Leist, Marcel

    2013-01-01

    Summary Metabolomics, the comprehensive analysis of metabolites in a biological system, provides detailed information about the biochemical/physiological status of a biological system, and about the changes caused by chemicals. Metabolomics analysis is used in many fields, ranging from the analysis of the physiological status of genetically modified organisms in safety science to the evaluation of human health conditions. In toxicology, metabolomics is the -omics discipline that is most closely related to classical knowledge of disturbed biochemical pathways. It allows rapid identification of the potential targets of a hazardous compound. It can give information on target organs and often can help to improve our understanding regarding the mode-of-action of a given compound. Such insights aid the discovery of biomarkers that either indicate pathophysiological conditions or help the monitoring of the efficacy of drug therapies. The first toxicological applications of metabolomics were for mechanistic research, but different ways to use the technology in a regulatory context are being explored. Ideally, further progress in that direction will position the metabolomics approach to address the challenges of toxicology of the 21st century. To address these issues, scientists from academia, industry, and regulatory bodies came together in a workshop to discuss the current status of applied metabolomics and its potential in the safety assessment of compounds. We report here on the conclusions of three working groups addressing questions regarding 1) metabolomics for in vitro studies 2) the appropriate use of metabolomics in systems toxicology, and 3) use of metabolomics in a regulatory context. PMID:23665807

  7. FISH PHYSIOLOGY, TOXICOLOGY, AND WATER QUALITY:

    Science.gov (United States)

    Twenty-one participants from Europe, North America and China convened in Chongqing, China, October 12-14, 2005, for the Eighth International Symposium in Fish Physiology, Toxicology and Water Quality. The subject of the meeting was "Hypoxia in vertebrates: Comparisons of terrestr...

  8. Toxicological requirements for risk assessment of shellfish ...

    African Journals Online (AJOL)

    There is increasing concern by consumers with regard to the health aspects and safety of foodstuffs. Most food additives and contaminants are controlled by regulatory authorities, with Acceptable Daily Intakes (ADIs) having been set on the basis of detailed acute short- and long-term toxicological studies. The situation with ...

  9. Phytochemical Screening, Antibacterial and Toxicological Activities ...

    African Journals Online (AJOL)

    The phytochemical screening, antibacterial and toxicological activities of extracts of the stem bark of Acacia senegal were investigated. The phytochemical analyses according to standard screening tests using conventional protocols revealed the presence of tannins, saponins and sterols in the stem bark of the plant.

  10. Collection of biological samples in forensic toxicology.

    Science.gov (United States)

    Dinis-Oliveira, R J; Carvalho, F; Duarte, J A; Remião, F; Marques, A; Santos, A; Magalhães, T

    2010-09-01

    Forensic toxicology is the study and practice of the application of toxicology to the purposes of the law. The relevance of any finding is determined, in the first instance, by the nature and integrity of the specimen(s) submitted for analysis. This means that there are several specific challenges to select and collect specimens for ante-mortem and post-mortem toxicology investigation. Post-mortem specimens may be numerous and can endow some special difficulties compared to clinical specimens, namely those resulting from autolytic and putrefactive changes. Storage stability is also an important issue to be considered during the pre-analytic phase, since its consideration should facilitate the assessment of sample quality and the analytical result obtained from that sample. The knowledge on degradation mechanisms and methods to increase storage stability may enable the forensic toxicologist to circumvent possible difficulties. Therefore, advantages and limitations of specimen preservation procedures are thoroughfully discussed in this review. Presently, harmonized protocols for sampling in suspected intoxications would have obvious utility. In the present article an overview is given on sampling procedures for routinely collected specimens as well as on alternative specimens that may provide additional information on the route and timing of exposure to a specific xenobiotic. Last, but not least, a discussion on possible bias that can influence the interpretation of toxicological results is provided. This comprehensive review article is intented as a significant help for forensic toxicologists to accomplish their frequently overwhelming mission.

  11. FISH PHYSIOLOGY, TOXICOLOGY, AND WATER QUALITY

    Science.gov (United States)

    Scientists from ten countries presented papers at the Fifth International Symposium on Fish Physiology, Toxicology, and Water Quality, which was held on the campus of the city University of Hong Kong on November 10-13, 1998. These Proceedings include 23 papers presented in sessi...

  12. Phytochemical analysis and toxicological evaluation of the ...

    African Journals Online (AJOL)

    Phytochemical analysis revealed the presence of tannins, Flavonoid, Alkaloids, Anthraquinone, Saponin and Cardiac glycosides. This work thus justifies the ethnomedicinal use of the plant in the treatment of anaemia and its safety profile. Keywords: Toxicological, Ethno toxicity, Hematological and phytochemical ...

  13. The rat incisor in toxicologic pathology

    NARCIS (Netherlands)

    Kuijpers, M.H.M.; Kooij, A.J. van de; Slootweg, P.J.

    1996-01-01

    Microscopic examination of the incisors of rats and mice may reveal toxicologically significant changes. First, the incisor morphology reflects the nutritional status of the animal: fluctuations of mineral metabolism and vitamin availability are disclosed by the rodent incisors, because the incisors

  14. A prospective toxicology analysis in alcoholics

    DEFF Research Database (Denmark)

    Thomsen, Jørgen Lange; Simonsen, Kirsten Wiese; Felby, Søren

    1997-01-01

    A prospective and comprehensive investigation was done on 73 medico–legal autopsies in alcoholics. The results of the toxicology analyses are described. Alcohol intoxication was the cause of death in 8%, combined alcohol/drug intoxication in 15% and drugs alone in 19%. Alcoholic ketoacidosis...

  15. Toxicology research for precautionary decision-making and the role of Human & Experimental Toxicology.

    Science.gov (United States)

    Grandjean, P

    2015-12-01

    A key aim of toxicology is the prevention of adverse effects due to toxic hazards. Therefore, the dissemination of toxicology research findings must confront two important challenges: one being the lack of information on the vast majority of potentially toxic industrial chemicals and the other being the strict criteria for scientific proof usually required for decision-making in regard to prevention. The present study ascertains the coverage of environmental chemicals in four volumes of Human & Experimental Toxicology and the presentation and interpretation of research findings in published articles. Links in SciFinder showed that the 530 articles published in four selected volumes between 1984 and 2014 primarily dealt with metals (126 links) and other toxicants that have received substantial attention in the past. Thirteen compounds identified by US authorities in 2006 as high-priority substances, for which toxicology documentation is badly needed, were not covered in the journal issues at all. When reviewing published articles, reliance on p values was standard, and non-significant findings were often called 'negative.' This tradition may contribute to the perceived need to extend existing research on toxic hazards that have already been well characterized. Several sources of bias towards the null hypothesis can affect toxicology research, but are generally not considered, thus adding to the current inclination to avoid false positive findings. In this regard, toxicology is particularly prone to bias because of the known paucity of false positives and, in particular, the existence of a vast number of toxic hazards which by default are considered innocuous due to lack of documentation. The Precautionary Principle could inspire decision-making on the basis of incomplete documentation and should stimulate a change in toxicology traditions and in toxicology research publication. © The Author(s) 2015.

  16. Potential subchronic food safety of the stacked trait transgenic maize GH5112E-117C in Sprague-Dawley rats.

    Science.gov (United States)

    Han, Shiwen; Zou, Shiying; He, Xiaoyun; Huang, Kunlun; Mei, Xiaohong

    2016-08-01

    The food safety of stacked trait genetically modified (GM) maize GH5112E-117C containing insect-resistance gene Cry1Ah and glyphosate-resistant gene G2-aroA was evaluated in comparison to non-GM Hi-II maize fed to Sprague-Dawley rats during a 90-day subchronic feeding study. Three different dietary concentrations (12.5, 25 and 50 %, w/w) of the GM maize were used or its corresponding non-GM maize. No biologically significant differences in the animals' clinical signs, body weights, food consumption, hematology, clinical chemistry, organ weights and histopathology were found between the stacked trait GM maize groups, and the non-GM maize groups. The results of the 90-day subchronic feeding study demonstrated that the stacked trait GM maize GH5112E-117C is as safe as the conventional non-GM maize Hi-II.

  17. An experimental study on the toxicity of several radionuclides inhaled at different doses

    International Nuclear Information System (INIS)

    Lafuma, J.; Nenot, J.C.; Morin, M.; Masse, R.; Metivier, H.; Nolibe, D.; Skupinski, W.

    1975-01-01

    For over 5 years investigations have been carried out on large lots of rats on the toxicological action of several inhaled radionuclides. Various physico chemical forms of α-emitting actinides and β-emitting lanthanides were used, respectively 239 Pu, 238 Pu, 241 Am, as oxide or nitrate solution at pH1, 244 Cm nitrate, and 144 Ce chloride and 141 Ce chloride and oxide. The activities deposited per gram of lung varied between 10nCi and 10μCi. The first effect observed was life-shortening. A comparison of the survival curves shows a heterogeneity factor whose values for the various radionuclides is given. Lung cancers were also observed. Rarely lung carcinomas were the cause of death, which was unknown and seemed to vary with the different compounds [fr

  18. Distance learning in toxicology: Australia's RMIT program

    International Nuclear Information System (INIS)

    Ahokas, Jorma; Donohue, Diana; Rix, Colin; Wright, Paul

    2005-01-01

    RMIT University was the first to offer a comprehensive Masters of Toxicology in Australasia 19 years ago. In 2001 the program was transformed into two stages, leading to a Graduate Diploma and Master of Applied Science in Toxicology. Now, these programs are fully online and suitable for graduates living and working anywhere in the world. The modular distance-learning courses are specifically designed to equip students with essential skills for entering fields such as chemical and drug evaluation; risk assessment of chemicals in the workplace; environmental and food toxicology. RMIT's online course delivery system has made it possible to deliver the toxicology programs, both nationally and internationally. The learning material and interactive activities (tests and quizzes, discussion boards, chat sessions) use Blackboard and WebBoard, each with a different educational function. Students log in to a Learning Hub to access their courses. The Learning Hub enables students to extend their learning beyond the classroom to the home, workplace, library and any other location with Internet access. The teaching staff log in to the Learning Hub to maintain and administer the online programs and courses which they have developed and/or which they teach. The Learning Hub is also a communication tool for students and staff, providing access to email, a diary and announcements. The early experience of delivering a full toxicology program online is very positive. However this mode of teaching continues to present many interesting technical, educational and cultural challenges, including: the design and presentation of the material; copyright issues; internationalisation of content; interactive participation; and the assessment procedures

  19. Subchronic inhalation of coal dust particulate matter 10 induces bronchoalveolar hyperplasia and decreases MUC5AC expression in male Wistar rats.

    Science.gov (United States)

    Kania, Nia; Setiawan, Bambang; Widjadjanto, Edi; Nurdiana, Nurdiana; Widodo, M Aris; Kusuma, H M S Chandra

    2014-10-01

    Coal dust is a pollutant found in coal mines that are capable of inducing oxidative stress and inflammation, but the effects on lung metaplasia as an early step of carcinogenesis remain unknown. The purpose of the present study was to evaluate the effects of PM10 coal dust on lung histology, MUC5AC expression, epidermal growth factor (EGF) expression, and epidermal growth factor receptor (EGFR) expression. An experimental study was done on male Wistar rats, which were divided into the following groups: control groups exposed to coal dust for 14 days (at doses of 6.25 mg/m(3), 12.5 mg/m(3), and 25 mg/m(3)), and the groups exposed to coal dust for 28 days (at doses of 6.25 mg/m(3), 12.5 mg/m(3), and 25 mg/m(3)). EGF expressions in rat lungs were measured by ELISA. EGFR and MUC5AC were measured by a confocal laser scanning microscope. The bronchoalveolar epithelial image of the group exposed to coal dust for 14 and 28 days showed a epithelial rearrangement, hyperplastic (metaplastic) goblet cells, and scattered massive inflammatory cells. The pulmonary parenchymal image of the group of exposed to coal dust for 14 and 28 days showed scattered inflammatory cells filling up the pulmonary alveolar networks, leading to an appearance of thickened parenchymal alveoli until emphysema-like structure. There was no significant difference in MUC5AC, EGF, and EGFR expressions for 14-d exposure (p>0.05). There was no significant difference in EGF and EGFR expressions for 28-d exposure (p>0.05), but there was a significant difference in MUC5AC expression (phyperplasia and rearrangement of epithelial cells which accompanied by decrease expression MUC5AC in male rats. Copyright © 2014 Elsevier GmbH. All rights reserved.

  20. A SUBCHRONIC INHALATION STUDY OF FISCHER 344 RATS EXPOSED TO 0, 0.4, 1.4 OR 4.0 PPM ACROLEIN

    International Nuclear Information System (INIS)

    KUTZMAN, R.S.

    1981-01-01

    Fischer 344 rats were exposed to 0.0, 0.4, 1.4, or 4.0 ppm acrolein for 62 days. The major objective of the study was to relate the results of a series of pulmonary function tests to biochemical and pathological alterations observed in the lung. Cytological and reproductive potential endpoints were also assessed after acrolein exposure. Rats were exposed to acrolein for 6 hours/day, 5 days/week for 62 days. Mortality was observed only in the 4.0 ppm chamber where 32 of 57 exposed males died; however, none of the 8 exposed females died. Most of the mortality occurred within the first 10 exposure days. Histologic examination indicated that the animals died of acute bronchopneumonia. The surviving males and females exposed to 4.0 ppm acrolein gained weight at a significantly slower rate than control animals. The growth of both sexes in the 0.4 and 1.4 ppm groups was similar to that of their respective controls. Histopathologic examination of animals after 62 days of exposure revealed bronchiolar epithelial necrosis and sloughing, bronchiolar edema with macrophages, and focal pulmonary edema in the 4.0 ppm group. These lesions were, in some cases, associated with edema of the trachea and peribronchial lymph nodes, and acute rhinitis which indicated an upper respiratory tract effect of acrolein. Of particular interest was the variability of response between rats in the 4.0 ppm group, some not affected at all while others were moderately affected. Intragroup variability in toxicity was also apparent in the 1.4 ppm exposure group where only 3 of 31 animals examined had lesions directly related to acrolein exposure. Extra respiratory organs appeared unaffected

  1. Two cases of methyl alcohol intoxication by sub-chronic inhalation and dermal exposure during aluminum CNC cutting in a small-sized subcontracted factory.

    Science.gov (United States)

    Ryu, Jia; Lim, Key Hwan; Ryu, Dong-Ryeol; Lee, Hyang Woon; Yun, Ji Young; Kim, Seoung-Wook; Kim, Ji-Hoon; Jung-Choi, Kyunghee; Kim, Hyunjoo

    2016-01-01

    Methyl alcohol poisoning has been mainly reported in community. Two cases of methyl alcohol poisoning occurred in a small-sized subcontracted factory which manufactured smartphone parts in Korea. One young female patient presented with dyspnea and visual disturbance. Another young male patient presented with visual disturbance and myalgia. They treated with sodium bicarbonate infusion and hemodialysis for metabolic acidosis. In addition, he received ethyl alcohol per oral treatment. Her and his urinary methyl alcohol concentration was detected as 7.632 mg/L, 46.8 mg/L, respectively, although they were treated hemodialysis. Results of the working environment measurement showed that the concentration of methyl alcohol (1030.1-2220.5 ppm) in the air exceeded the time weighted average (200 ppm). They were diagnosed with optic neuropathy due to methyl alcohol poisoning and still have visual impairment. Workers who hired as dispatched employees in a small-sized subcontracted factory were exposed to high concentrations of methyl alcohol. The workplace had poor ventilation system. In addition, workers did not wear proper personal protect equipment. Working environment measurement and annual chekups for workers were not performed. They were in a blind spot to occupational safety and health. More attention is needed to protect vulnerable workers' health.

  2. New magnetostratigraphy for the Olduvai Subchron in the Koobi Fora Formation, northwest Kenya, with implications for early Homo

    Science.gov (United States)

    Lepre, Christopher J.; Kent, Dennis V.

    2010-02-01

    A problematic magnetostratigraphy for the Koobi Fora Formation has contributed to debates on the evolutionary implications for early hominin fossils. To address this, 50 independent samples distributed over a nearly 63-m-thick interval were collected from the lower-middle KBS Member type section in fossil collection Area 102, northeast Turkana Basin. Characteristic directions obtained by thermal demagnetization define a coherent magnetostratigraphy that is supported by alternating-field studies on 28 sister specimens and the prior tephrochronological framework. Two long polarity intervals were recognized, each 30-40 m in thickness, and interpreted as the upper part of the normal polarity Olduvai Subchron and the overlying reverse polarity Matuyama Chron. The end Olduvai consists of a normal-reverse-normal polarity sequence occurring over a thickness of at least 1 m but perhaps up to 5 m, suggesting that this subchron has a short reverse interval in its uppermost part. Such a fine-scale structure also has been reported from several other sites, like the Pliocene-Pleistocene boundary and point stratotype section at Vrica, Italy, which serves as a basis for formally delimiting three temporally discrete polarity subintervals for the Olduvai Subchron. These paleomagnetic results that place the upper boundary of the Olduvai at ˜ 48 m above the base of the KBS Member, coupled with published radioisotopic dates, firmly secure the age of partial cranium KNM-ER 3733 in the interval 1.78-1.48 Ma, with an interpolated age of ˜ 1.7 Ma, giving this fossil the most unambiguous numerical-age constraints, as compared to the oldest Homo cranial remains from Europe and Asia. Nonetheless, assured placement of the top of the Olduvai Subchron in the KBS Member is not sufficient in the face of other uncertainties to influence conventional interpretations of the timing and direction for the global dispersal of early Homo erectus.

  3. Memory and brain-derived neurotrophic factor after subchronic or chronic amphetamine treatment in an animal model of mania.

    Science.gov (United States)

    Fries, Gabriel R; Valvassori, Samira S; Bock, Hugo; Stertz, Laura; Magalhães, Pedro Vieira da Silva; Mariot, Edimilson; Varela, Roger B; Kauer-Sant'Anna, Marcia; Quevedo, João; Kapczinski, Flávio; Saraiva-Pereira, Maria Luiza

    2015-09-01

    Progression of bipolar disorder (BD) has been associated with cognitive impairment and changes in neuroplasticity, including a decrease in serum brain-derived neurotrophic factor (BDNF). However, no study could examine BDNF levels directly in different brain regions after repeated mood episodes to date. The proposed animal model was designed to mimic several manic episodes and evaluate whether the performance in memory tasks and BDNF levels in hippocampus, prefrontal cortex, and amygdala would change after repeated amphetamine (AMPH) exposure. Adult male Wistar rats were divided into subchronic (AMPH for 7 days) and chronic groups (35 days), mimicking manic episodes at early and late stages of BD, respectively. After open field habituation or inhibitory avoidance test, rats were killed, brain regions were isolated, and BDNF mRNA and protein levels were measured by quantitative real-time PCR and ELISA, respectively. AMPH impaired habituation memory in both subchronic and chronic groups, and the impairment was worse in the chronic group. This was accompanied by increased Bdnf mRNA levels in the prefrontal cortex and amygdala region, as well as reduced BDNF protein in the hippocampus. In the inhibitory avoidance, AMPH significantly decreased the change from training to test when compared to saline. No difference was observed between subchronic and chronic groups, although chronically AMPH-treated rats presented increased Bdnf mRNA levels and decreased protein levels in hippocampus when compared to the subchronic group. Our results suggest that the cognitive impairment related to BD neuroprogression may be associated with BDNF alterations in hippocampus, prefrontal cortex, and amygdala. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Air pollution & the brain: Subchronic diesel exhaust exposure causes neuroinflammation and elevates early markers of neurodegenerative disease

    OpenAIRE

    McDonald Jacob; Surace Michael J; Levesque Shannon; Block Michelle L

    2011-01-01

    Abstract Background Increasing evidence links diverse forms of air pollution to neuroinflammation and neuropathology in both human and animal models, but the effects of long-term exposures are poorly understood. Objective We explored the central nervous system consequences of subchronic exposure to diesel exhaust (DE) and addressed the minimum levels necessary to elicit neuroinflammation and markers of early neuropathology. Methods Male Fischer 344 rats were exposed to DE (992, 311, 100, 35 a...

  5. Databases applicable to quantitative hazard/risk assessment-Towards a predictive systems toxicology

    International Nuclear Information System (INIS)

    Waters, Michael; Jackson, Marcus

    2008-01-01

    The Workshop on The Power of Aggregated Toxicity Data addressed the requirement for distributed databases to support quantitative hazard and risk assessment. The authors have conceived and constructed with federal support several databases that have been used in hazard identification and risk assessment. The first of these databases, the EPA Gene-Tox Database was developed for the EPA Office of Toxic Substances by the Oak Ridge National Laboratory, and is currently hosted by the National Library of Medicine. This public resource is based on the collaborative evaluation, by government, academia, and industry, of short-term tests for the detection of mutagens and presumptive carcinogens. The two-phased evaluation process resulted in more than 50 peer-reviewed publications on test system performance and a qualitative database on thousands of chemicals. Subsequently, the graphic and quantitative EPA/IARC Genetic Activity Profile (GAP) Database was developed in collaboration with the International Agency for Research on Cancer (IARC). A chemical database driven by consideration of the lowest effective dose, GAP has served IARC for many years in support of hazard classification of potential human carcinogens. The Toxicological Activity Profile (TAP) prototype database was patterned after GAP and utilized acute, subchronic, and chronic data from the Office of Air Quality Planning and Standards. TAP demonstrated the flexibility of the GAP format for air toxics, water pollutants and other environmental agents. The GAP format was also applied to developmental toxicants and was modified to represent quantitative results from the rodent carcinogen bioassay. More recently, the authors have constructed: 1) the NIEHS Genetic Alterations in Cancer (GAC) Database which quantifies specific mutations found in cancers induced by environmental agents, and 2) the NIEHS Chemical Effects in Biological Systems (CEBS) Knowledgebase that integrates genomic and other biological data including

  6. Organic Trace Compounds as Emisions of Incineration Plants and their Toxicological and Ecotoxicological Classification - Part 2. Toxicological and ecotoxicological classification; Organische Spurenstoffe als Emissionen aus Verbrennungsanlagen und deren humantoxikologische und oekotoxikologische Einordnung. T. 2. Humantoxikologische und oekotoxikologische Einordnung

    Energy Technology Data Exchange (ETDEWEB)

    Kaiser, G.; Wiedmann, T.; Ballschmiter, K.

    1998-02-01

    In this report (`Organic Trace Compounds as Emissions of Incineration Plants and their Toxicological and Ecotoxicologial Classification - Part 2: Toxicological and Ecotoxicological Classification`) emissions of organic compounds, measured from German municipal waste incineration plants, are compared with toxicological and ecotoxicological data, limits and threshold values and environmental baseline levels. Emission data of other combustion processes are integrated if available. A modern waste incineration plant, observing German emission regulations, emits less of most substances reported here than other industrial processes or e.g. the combustion of wood or coal. (orig.) [Deutsch] Im vorliegenden Arbeitsbericht (`Organische Spurenstoffe als Emissionen aus Verbrennungsanlagen und deren humantoxikologische und oekotoxikologische Einordnung - Teil 2: Humantoxikologische und oekotoxikologische Einordnung`) werden die realen organischen Emissionen von Muellverbrennungsanlagen in groesstmoeglicher stofflicher Differenzierung toxikologisch eingeordnet. Hierzu werden die Daten mit human-/oekotoxikologischen Kenngroessen, Grenz- und Orientierungswerten sowie mit der Hintergrundbelastung verglichen und die inhalative Zusatzbelastung wird berechnet. Diese liegt fuer alle Stoffe im Bereich von 10{sup -9} bis 10{sup -1} Prozent. Eine Ausnahme bilden die Phthalsaeureester mit einem Spitzenwert fuer die Zusatzbelastung von 6,5%. Wenn vorhanden, werden die Emissionsdaten von anderen Verbrennungsprozessen mit in die Einordnung aufgenommen. Von vielen Substanzklassen wird bei einer Abfallverbrennungsanlage, die die Grenzwerte der 17. BImSchV einhaelt, weniger an die Umgebungsluft abgegeben als bei anderen industriellen Prozessen oder z.B. bei der Verbrennung von Kohle oder Holz. (orig.)

  7. Acute and subchronic toxicity as well as mutagenic evaluation of essential oil from turmeric (Curcuma longa L).

    Science.gov (United States)

    Liju, Vijayasteltar B; Jeena, Kottarapat; Kuttan, Ramadasan

    2013-03-01

    The present study investigated the acute, subchronic and genotoxicity of turmeric essential oil (TEO) from Curcuma longa L. Acute administration of TEO was done as single dose up to 5 g of TEO per kg body weight and subchronic toxicity study for thirteen weeks was done by daily oral administration of TEO at doses 0.1, 0.25 and 0.5 g/kg b.wt. in Wistar rats. There were no mortality, adverse clinical signs or changes in body weight; water and food consumption during acute as well as subchronic toxicity studies. Indicators of hepatic function such as aspartate aminotransferase (AST), alanine amino transferase (ALT) and alkaline phosphatase (ALP) were unchanged in treated animals compared to untreated animals. Oral administration of TEO for 13 weeks did not alter total cholesterol, triglycerides, markers of renal function, serum electrolyte parameters and histopathology of tissues. TEO did not produce any mutagenicity to Salmonella typhimurium TA-98, TA-100, TA-102 and TA-1535 with or without metabolic activation. Administration of TEO to rats (1 g/kg b.wt.) for 14 days did not produce any chromosome aberration or micronuclei in rat bone marrow cells and did not produce any DNA damage as seen by comet assay confirming the non toxicity of TEO. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Acute and subchronic toxicity study of the water extract from dried fruits of Piper nigrum L. in rats

    Directory of Open Access Journals (Sweden)

    Kanjana Jaijoy

    2007-03-01

    Full Text Available The study was carried out to evaluate acute and subchronic toxicities of the water extract from the dried fruits of Piper nigrum L. A single oral administration of the extract at a dose of 5,000 mg/kg body weight (5 male, 5 female did not produce signs of toxicity, behavioral changes, mortality, changes on gross appearance or histopathological changes of internal organs. The subchronic toxicity was determined by oral feeding both male and female rats (10 male, 10 female daily with the test substance at the doses of 300, 600 and 1,200 mg/kg body weight continuously for 90 days. The examinations of signs, animal behavior and health monitoring showed no abnormalities in the test groups as compared to the controls. The test and control groups (on the 90th day and the satellite group (on the 118th day were analyzed by measuring their final body and organ weights, taking necropsy, and examining hematology, blood clinical chemistry and histopathology. The results suggest that the water extract from the dried fruits of P. nigrum does not cause acute or subchronic toxicities in either male or female rats.

  9. Acute and subchronic toxicity of the antitumor agent rhodium (II citrate in Balb/c mice after intraperitoneal administration

    Directory of Open Access Journals (Sweden)

    Marcella L.B. Carneiro

    2015-01-01

    Full Text Available This study aimed to investigate potential acute and subchronic toxicity of rhodium (II citrate in female Balb/c mice after intraperitoneal injections. In the acute test, independent groups received five doses; the highest dose (107.5 mg/kg was equivalent to 33 times that used in our previous reports. The other doses were chosen as proportions of the highest, being 80.7 (75%, 53.8 (50%, 26.9 (25% or 13.8 mg/kg (12.5%. Animals were monitored over 38 days and no severe signs of toxicity were observed, according to mortality, monitoring of adverse symptoms, hematological, biochemical and genotoxic parameters. We conclude that the median lethal dose (LD50 could be greater than 107.5 mg/kg. In the subchronic test, five doses of Rh2Cit (80, 60, 40, 20 or 10 mg/kg were evaluated and injections were conducted on alternate days, totaling five applications per animal. Paclitaxel (57.5 mg/kg and saline solution were controls. Clinical observations, histopathology of liver, lung and kidneys and effects on hematological, biochemistry and genotoxic records indicated that Rh2Cit induced no severe toxic effects, even at an accumulated dose up to 400 mg/kg.We suggest Rh2Cit has great potential as an antitumor drug without presenting acute and subchronic toxicity.

  10. Acute and subchronic toxicity study of the water extract from root of Imperata cylindrica (Linn. Raeusch. in rats

    Directory of Open Access Journals (Sweden)

    Siharat Chunlaratthanaphorn

    2007-03-01

    Full Text Available The water extract from root of Imperata cylindrica (Linn. Raeusch. was studied for acute and subchronic toxicities. The extract at a single dose of 5,000 mg/kg was administered orally to female and male rats (5 male, 5 female. After 14 days, signs and behavioral changes, mortality, gross and histopathological changes of internal organs were examined. The extract did not produce signs of toxicity. For the subchronic toxicity test, the extract at doses of 300, 600 and 1,200 mg/kg body weight was orally administered to rats daily for 90 days (10 male, 10 female. The observation of signs, behavior and health status showed no abnormality in the test groups as compared with the controls. At the end of the study, necropsy and histopathology examination were performed in all animals in the control group, the test groups and the satellite group in which the extract was discontinued for another 28 days. Body and organ weights, hematological and blood clinical chemistry were also examined. The results suggest that the water extract of Imperata cylindrica (Linn. Raeusch does not cause acute and subchronic toxicities in rats.

  11. A comprehensive evaluation of the toxicology of cigarette ingredients: carbohydrates and natural products.

    Science.gov (United States)

    Coggins, Christopher R E; Wagner, Karl A; Werley, Michael S; Oldham, Michael J

    2011-06-01

    Eleven carbohydrates and natural product ingredients were added individually to experimental cigarettes. A battery of tests was used to compare toxicity of mainstream smoke from these experimental cigarettes to matched control cigarettes without test ingredients. Smoke fractions from each cigarette type were evaluated using analytical chemistry; in vitro cytotoxicity (neutral red uptake) and in vitro bacterial (Salmonella) mutagenicity (five strains) testing. For 10 ingredients (β-cyclodextrin, cleargum, D-sorbitol, high fructose corn syrup, honey, invert sugar, maltodextrin, molasses, raisin juice concentrate, and sucrose), 90-day nose-only smoke inhalation studies using rats were also performed. In general, addition of each ingredient in experimental cigarettes resulted in minimal changes in smoke chemistry; the exceptions were D-sorbitol and sucrose, where reductions in amount of 60% to 80% of control values for some smoke constituents were noted. Additionally, each ingredient resulted in small increases in smoke formaldehyde concentrations. Except for a reduction in cytotoxicity by inclusion of maltodextrin and an increase by inclusion of plum juice concentrate, the cytotoxicity and mutagenicity results were unaffected by addition of the other ingredients in experimental cigarettes. There were also very few statistically significant differences within any of the 10 inhalation studies, and when present, the differences were largely sporadic and inconsistent between sexes. The carbohydrates and natural products tested here as ingredients in experimental cigarettes as a class increased formaldehyde, but resulted in minimal toxicological responses, even at high inclusion levels compared with the levels used in commercial cigarette products.

  12. A comprehensive evaluation of the toxicology of cigarette ingredients: aliphatic and aromatic carboxylic acids.

    Science.gov (United States)

    Coggins, Christopher R E; Liu, Jianmin; Merski, Jerome A; Werley, Michael S; Oldham, Michael J

    2011-06-01

    Aromatic and aliphatic carboxylic acids are present in tobacco and tobacco smoke. A battery of tests was used to compare the toxicity of mainstream smoke from experimental cigarettes containing eight aromatic and aliphatic carboxylic acids and the salt of one acid that were added individually at three different levels (lowest and highest target inclusions were 100 and 90,000 ppm, respectively). Mainstream smoke from cigarettes containing each of the test ingredients was evaluated using analytical chemistry and assays to measure in vitro cytotoxicity (neutral red uptake) and Salmonella (five strains) mutagenicity. For four of the compounds (citric, lactic, benzoic acids, and sodium benzoate), 90-day rodent inhalation studies were also performed. Although sporadic statistically significant differences in some experimental cigarette smoke constituents occurred, none resulted in significant changes in mutagenicity or cytotoxicity responses, nor in responses measured in the inhalation studies, except for lactic acid (LA). Inclusion of LA resulted in dose-dependent increase in water and caused a dose-dependent decrease in cytotoxicity. Incorporation of LA into cigarettes resulted in several dose-related reductions in histopathology, which were largely restricted to the nasal passages. Incorporation of LA also ameliorated some of the typical decrease in body weight gain seen in cigarette smoke-exposed rats. Inclusion of these ingredients at exaggerated use levels resulted in sporadic dose-related and treatment effects for some smoke constituents, but no toxicological response was noted in the in vitro and in vivo tests performed.

  13. On-line sources of toxicological information in Canada

    International Nuclear Information System (INIS)

    Racz, William J.; Ecobichon, Donald J.; Baril, Marc

    2003-01-01

    This paper will provide an overview of the on-line resources available in toxicology in Canada. It will describe a brief history of The Society of Toxicology of Canada, with reference to other societies and also provide information on education, research and other resources related to toxicology. Toxicology in Canada emerged as a distinct and vibrant discipline following the thalidomide tragedy of the 1960s. In the pharmaceutical industry and government, toxicology was readily established as an essential component of drug development and safety, and as the need for toxicologists expanded, training programs were established, usually in collaboration with departments of pharmacology. In the last two to three decades other disciplines, environmental biology, analytical chemistry and epidemiology joined the ranks of toxicology. The on-line sources of toxicology information are rapidly expanding. This article describes those sources considered by the authors to be important from a national and international perspective. The majority of these sources are professional organizations and government agencies

  14. Inhaled antibiotics for lower airway infections.

    Science.gov (United States)

    Quon, Bradley S; Goss, Christopher H; Ramsey, Bonnie W

    2014-03-01

    Inhaled antibiotics have been used to treat chronic airway infections since the 1940s. The earliest experience with inhaled antibiotics involved aerosolizing antibiotics designed for parenteral administration. These formulations caused significant bronchial irritation due to added preservatives and nonphysiologic chemical composition. A major therapeutic advance took place in 1997, when tobramycin designed for inhalation was approved by the U.S. Food and Drug Administration (FDA) for use in patients with cystic fibrosis (CF) with chronic Pseudomonas aeruginosa infection. Attracted by the clinical benefits observed in CF and the availability of dry powder antibiotic formulations, there has been a growing interest in the use of inhaled antibiotics in other lower respiratory tract infections, such as non-CF bronchiectasis, ventilator-associated pneumonia, chronic obstructive pulmonary disease, mycobacterial disease, and in the post-lung transplant setting over the past decade. Antibiotics currently marketed for inhalation include nebulized and dry powder forms of tobramycin and colistin and nebulized aztreonam. Although both the U.S. Food and Drug Administration and European Medicines Agency have approved their use in CF, they have not been approved in other disease areas due to lack of supportive clinical trial evidence. Injectable formulations of gentamicin, tobramycin, amikacin, ceftazidime, and amphotericin are currently nebulized "off-label" to manage non-CF bronchiectasis, drug-resistant nontuberculous mycobacterial infections, ventilator-associated pneumonia, and post-transplant airway infections. Future inhaled antibiotic trials must focus on disease areas outside of CF with sample sizes large enough to evaluate clinically important endpoints such as exacerbations. Extrapolating from CF, the impact of eradicating organisms such as P. aeruginosa in non-CF bronchiectasis should also be evaluated.

  15. Toxicology: a discipline in need of academic anchoring--the point of view of the German Society of Toxicology.

    Science.gov (United States)

    Gundert-Remy, U; Barth, H; Bürkle, A; Degen, G H; Landsiedel, R

    2015-10-01

    The paper describes the importance of toxicology as a discipline, its past achievements, current scientific challenges, and future development. Toxicological expertise is instrumental in the reduction of human health risks arising from chemicals and drugs. Toxicological assessment is needed to evaluate evidence and arguments, whether or not there is a scientific base for concern. The immense success already achieved by toxicological work is exemplified by reduced pollution of air, soil, water, and safer working places. Predominantly predictive toxicological testing is derived from the findings to assess risks to humans and the environment. Assessment of the adversity of molecular effects (including epigenetic effects), the effects of mixtures, and integration of exposure and biokinetics into in vitro testing are emerging challenges for toxicology. Toxicology is a translational science with its base in fundamental science. Academic institutions play an essential part by providing scientific innovation and education of young scientists.

  16. Acute renal failure from inhalation of mycotoxins.

    Science.gov (United States)

    Di Paolo, N; Guarnieri, A; Loi, F; Sacchi, G; Mangiarotti, A M; Di Paolo, M

    1993-01-01

    Mysterious deaths of archeologists after opening Egyptian tombs have been suspected to be secondary to inhalation of mycotoxin, however, the hypothesis has never been verified. Recently, we observed a case of acute renal failure (ARF) undeniably due to inhalation of ochratoxin of Aspergillus ochraceus. After spending 8 h in a granary which had been closed for several months, a farmer and his wife suffered temporary respiratory distress; 24 h later, the woman developed nonoliguric ARF and biopsy revealed tubulonecrosis which healed in 24 days. Toxic substances were not found, but a strain of A. ochraceus producing ochratoxin was isolated from the wheat.

  17. Inhaled mycotoxins lead to acute renal failure.

    Science.gov (United States)

    Di Paolo, N; Guarnieri, A; Garosi, G; Sacchi, G; Mangiarotti, A M; Di Paolo, M

    1994-01-01

    Mysterious deaths of archeologists after opening Egyptian tombs have been suspected, but never proved, to be secondary to inhalation of mycotoxin. We observed a case of acute renal failure (ARF) due to inhalation of ochratoxin A produced by a mould of the species Aspergillus ochraceus. After working 8 h in a granary closed for several months, a farmer and his wife suffered respiratory distress; the woman developed non-oliguric ARF and biopsy revealed tubulonecrosis. A strain of Aspergillus ochraceus producing ochratoxin was isolated from the wheat.

  18. Impact of online toxicology training on health professionals: the Global Educational Toxicology Uniting Project (GETUP).

    Science.gov (United States)

    Wong, Anselm; Vohra, Rais; Dawson, Andrew H; Stolbach, Andrew

    2017-11-01

    The Global Educational Toxicology Uniting Project (GETUP), supported by the American College of Medical Toxicology, links countries with and without toxicology services via distance education with the aim to improve education. Due to the lack of toxicology services in some countries there is a knowledge gap in the management of poisonings. We describe our experience with the worldwide delivery of an online introductory toxicology curriculum to emergency doctors and other health professionals treating poisoned patients. We delivered a 15-module introductory Internet-based toxicology curriculum to emergency doctors and health professionals, conducted from August to December 2016. This Internet-based curriculum was adapted from one used to teach emergency residents toxicology in the United States. Modules covered themes such as pharmaceutical (n = 8), toxidromes (n = 2) and agrochemicals (n = 5) poisoning. Participants completed pre-test and post-test multiple choice questions (MCQs) before and after completing the online module, respectively, throughout the course. We collected information on participant demographics, education and training, and perception of relevance of the curriculum. Participants gave feedback on the course and how it affected their practice. One hundred and thirty-six health professionals from 33 countries participated in the course: 98 emergency doctors/medical officers, 25 physicians, eight pharmacists/poisons information specialists, two toxicologists, two medical students and one nurse. Median age of participants was 34 years. Median number of years postgraduate was seven. Ninety (65%) had access to either a poisons information centre over the phone or toxicologist and 48 (35%) did not. All participants expected the course to help improve their knowledge. Overall median pre-module MCQ scores were 56% (95%CI: 38, 75%) compared to post-module MCQ scores median 89% (95% CI: 67, 100%) (p education to health professionals treating

  19. Inhaled medication and inhalation devices for lung disease in patients with cystic fibrosis: A European consensus

    DEFF Research Database (Denmark)

    Heijerman, Harry; Westerman, Elsbeth; Conway, Steven

    2009-01-01

    , mucolytics/mucous mobilizers, anti-inflammatory drugs, bronchodilators and combinations of solutions. Additionally, we review the current knowledge on devices for inhalation therapy with regard to optimal particle sizes and characteristics of wet nebulisers, dry powder and metered dose inhalers. Finally, we...... review the current status of inhaled medication in CF, including the mechanisms of action of the various drugs, their modes of administration and indications, their effects on lung function, exacerbation rates, survival and quality of life, as well as side effects. Specifically we address antibiotics...

  20. Cow Dung Ingestion and Inhalation Dependence: A Case Report

    Science.gov (United States)

    Khairkar, Praveen; Tiple, Prashant; Bang, Govind

    2009-01-01

    Although abuse of several unusual inhalants had been documented, addiction to cow dung fumes or their ashes has not been reported in medical literature as yet. We are reporting a case of cow dung dependence in ingestion and inhalational form.

  1. Social stigma stops adolescents from using inhalers for asthma.

    Science.gov (United States)

    2017-07-10

    Forgetfulness, poor routines, inadequate inhaler technique, organisational difficulties and families not understanding or accepting their children's asthma are described as barriers to the use of inhalers among adolescents with asthma.

  2. Antiepileptogenic Effect of Subchronic Palmitoylethanolamide Treatment in a Mouse Model of Acute Epilepsy

    Directory of Open Access Journals (Sweden)

    Julia M. Post

    2018-03-01

    .c. injection was recently shown to most closely mimic human TLE, while systemic KA administration causes more widespread pathological damage, both in brain and periphery. To explore the potential of PEA to exert therapeutic effects both in brain and periphery, acute and subchronic administration of PEA by intraperitoneal (i.p. injection was assessed on mice with systemically administered KA. Specifically, we investigated: (i neuroprotective and anticonvulsant properties of acute and subchronic PEA treatment in KA-induced seizure models, and (ii temporal dynamics of eCB and eicosanoid (eiC levels in hippocampus and plasma over 180 min post seizure induction in PEA-treated and non-treated KA-injected mice vs. vehicle injected mice. Finally, we compared the systemic PEA treatment with, and in combination with, pharmacological blockade of fatty acid amide hydrolase (FAAH in brain and periphery, in terms of anticonvulsant properties and modulation of eCBs and eiCs. Here, we demonstrate that subchronic administration of PEA significantly alleviates seizure intensity, promotes neuroprotection and induces modulation of the plasma and hippocampal eCB and eiC levels in systemic KA-injected mice.

  3. Degeneration and recovery of rat olfactory epithelium following inhalation of dibasic esters.

    Science.gov (United States)

    Keenan, C M; Kelly, D P; Bogdanffy, M S

    1990-08-01

    Dibasic esters (DBE) are solvent mixtures used in the paint and coating industry. To evaluate the potential subchronic toxicity of DBE, groups of male and female rats were exposed for periods of up to 13 weeks to DBE concentrations of 0, 20, 76, or 390 mg/m3. After approximately 7 and 13 weeks of exposure, 10 rats per sex per group were subjected to clinical chemical, hematological, and urine analyses. Following 7 or 13 weeks of exposure, 10 or 20 rats per sex per group, respectively, were euthanized. An additional 10 rats were euthanized following a 6-week recovery period. A standard profile of tissues, including four levels of nasal cavity, was evaluated histopathologically. After 7 weeks of exposure, slight degeneration of the olfactory epithelium was observed in both male and female rats at 76 and 390 mg/m3. After 13 weeks, degeneration of the olfactory epithelium was present at all DBE concentrations in female rats, but only at the mid and high concentrations in male rats. The severity and incidence of the lesions were concentration related for both sexes with female rats being more sensitive than males. Following the recovery period, histological changes compatible with repair in the olfactory mucosa included an absence of degeneration, focal disorganization of the olfactory epithelium, and respiratory metaplasia. All other tissues were macroscopically normal. No other signs of toxicity were indicated by the other parameters evaluated. Inhalation studies of other esters demonstrate similar pathology in the olfactory epithelium. Since olfactory mucosa is rich in carboxylesterase activity, acids may be the toxic metabolites of these compounds. This hypothetical mechanism may explain the sensitivity of olfactory tissue to the effects of DBE.

  4. Recreational inhalation of butane and propane in adolescents: Two forensic cases of accidental death.

    Science.gov (United States)

    Sironi, Luca; Amadasi, Alberto; Zoja, Riccardo

    2016-09-01

    The recreational use of inhalants is a fairly widespread habit among adolescents because of the ease of availability and methods of assumption. Their use is however not free of risks, both for direct toxicity on several target organs and for a mechanism of gas replacement with lack of oxygen. The first case concerns a 12-year-old boy who died suddenly after sniffing a mix of butane and propane contained in a can of air freshener. The second case concerns a 14-year-old boy who died by acute poisoning by the same mixture contained in a refill for lighters. High concentrations of the compounds were found in the tissues by analysis with gas chromatography-mass spectrometry. The compounds found in tissues and biological fluids were perfectly compatible with those contained in the containers used for the inhalation. The mechanisms of death were therefore assessed in a combination of the direct toxicity of the compound and oxygen replacement, thus highlighting the crucial help that toxicological analyses can provide in such cases. Copyright © 2016. Published by Elsevier Ireland Ltd.

  5. Inflammatory and Vasoactive Effects of Serum Following Inhalation of Varied Complex Mixtures.

    Science.gov (United States)

    Aragon, Mario J; Chrobak, Izabela; Brower, Jeremy; Roldan, Luis; Fredenburgh, Laura E; McDonald, Jacob D; Campen, Matthew J

    2016-04-01

    Chronic cardiovascular disease is associated with air pollution exposure in epidemiology and toxicology studies. Inhaled toxicants can induce changes in serum bioactivity that impact endothelial inflammatory gene expression in vitro and impair vasorelaxation ex vivo, which are common precursors to atherosclerosis. Comparisons between single pollutants and common combustion mixtures, in terms of driving such serum inflammatory and vasoactive effects, have not been characterized. Healthy C57BL/6 mice were exposed to a single 6-h period of contrasting pollutant atmospheres: road dust, mixed vehicle emissions (MVE; a combination of gasoline and diesel engine emissions) particulate matter, mixed vehicle emissions gases, road dust plus ozone, road dust plus MVE, and hardwood smoke. Serum obtained from mice 24 h after these exposures was used as a stimulus to assess inflammatory potential in two assays: incubated with primary murine cerebrovascular endothelial cells for 4 h to measure inflammatory gene expression or applied to naïve aortic rings in an ex vivo myographic preparation. Road dust and wood smoke exposures were most potent at inducing inflammatory gene expression, while MVE atmospheres and wood smoke were most potent at impairing vasorelaxation to acetylcholine. Responses are consistent with recent reports on MVE toxicity, but reveal novel serum bioactivity related to wood smoke and road dust. These studies suggest that the compositional changes in serum and resultant bioactivity following inhalation exposure to pollutants may be highly dependent on the composition of mixtures.

  6. Studies of the contribution of respiratory tract metabolism to the toxicity of inhaled chemicals

    International Nuclear Information System (INIS)

    Dahl, A.R.; Petridou-Fischer, J.; Sabourin, P.J.; Whaley, S.; Bond, J.A.

    1987-01-01

    Efforts to identify specific nasal enzymes are reported. The nasal enzymes identified and characterized within this project include the cytochromes P-450, primary xenobiotic metabolizing enzymes for PAH's, nitrosamines, some halogenated compounds, alkenes, alkanes, and a large variety of other organic compounds. In addition, flavin containing monooxygenase (FMO), has been identified in the nasal cavity and characterized. Carboxylesterases, and rhodanese have also been found in the nasal cavity. Other nasal enzymes identified include: catechol methyltransferases, phenol methyltransferases, epoxide hydrolase and glutathione and glucuronyl transferases. Each of these enzyme systems may have important toxicological effects on inhaled materials. The authors have tested the ability of nasal enzymes to metabolize substrates in vivo. In these experiments, radiolabeled substances were placed on the nasal mucosas of monkeys, dogs, or Syrian hamsters. Mucus was then collected and analyzed for metabolites. It was found that benzo(a)pyrene and dihydrosafrole are both metabolized on the nasal surface following instillation by this method. Currently, experiments are planned to test the role of nasal enzymes in the fate of inhaled materials

  7. Nano-technology and nano-toxicology.

    Science.gov (United States)

    Maynard, Robert L

    2012-01-01

    Rapid developments in nano-technology are likely to confer significant benefits on mankind. But, as with perhaps all new technologies, these benefits are likely to be accompanied by risks, perhaps by new risks. Nano-toxicology is developing in parallel with nano-technology and seeks to define the hazards and risks associated with nano-materials: only when risks have been identified they can be controlled. This article discusses the reasons for concern about the potential effects on health of exposure to nano-materials and relates these to the evidence of the effects on health of the ambient aerosol. A number of hypotheses are proposed and the dangers of adopting unsubstantiated hypotheses are stressed. Nano-toxicology presents many challenges and will need substantial financial support if it is to develop at a rate sufficient to cope with developments in nano-technology.

  8. Avian models in teratology and developmental toxicology.

    Science.gov (United States)

    Smith, Susan M; Flentke, George R; Garic, Ana

    2012-01-01

    The avian embryo is a long-standing model for developmental biology research. It also has proven utility for toxicology research both in ovo and in explant culture. Like mammals, avian embryos have an allantois and their developmental pathways are highly conserved with those of mammals, thus avian models have biomedical relevance. Fertile eggs are inexpensive and the embryo develops rapidly, allowing for high-throughput. The chick genome is sequenced and significant molecular resources are available for study, including the ability for genetic manipulation. The absence of a placenta permits the direct study of an agent's embryotoxic effects. Here, we present protocols for using avian embryos in toxicology research, including egg husbandry and hatch, toxicant delivery, and assessment of proliferation, apoptosis, and cardiac structure and function.

  9. Systems Toxicology: The Future of Risk Assessment.

    Science.gov (United States)

    Sauer, John Michael; Hartung, Thomas; Leist, Marcel; Knudsen, Thomas B; Hoeng, Julia; Hayes, A Wallace

    2015-01-01

    Risk assessment, in the context of public health, is the process of quantifying the probability of a harmful effect to individuals or populations from human activities. With increasing public health concern regarding the potential risks associated with chemical exposure, there is a need for more predictive and accurate approaches to risk assessment. Developing such an approach requires a mechanistic understanding of the process by which xenobiotic substances perturb biological systems and lead to toxicity. Supplementing the shortfalls of traditional risk assessment with mechanistic biological data has been widely discussed but not routinely implemented in the evaluation of chemical exposure. These mechanistic approaches to risk assessment have been generally referred to as systems toxicology. This Symposium Overview article summarizes 4 talks presented at the 35th Annual Meeting of the American College of Toxicology. © The Author(s) 2015.

  10. Regulated necrosis and its implications in toxicology.

    Science.gov (United States)

    Aki, Toshihiko; Funakoshi, Takeshi; Uemura, Koichi

    2015-07-03

    Recent research developments have revealed that caspase-dependent apoptosis is not the sole form of regulated cell death. Caspase-independent, but genetically regulated, forms of cell death include pyroptosis, necroptosis, parthanatos, and the recently discovered ferroptosis and autosis. Importantly, regulated necrosis can be modulated by small molecule inhibitors/activators, confirming the cell autonomous mechanism of these forms of cell death. The success of small molecule-mediated manipulation of regulated necrosis has produced great changes in the field of cell death research, and has also brought about significant changes in the fields of pharmacology as well as toxicology. In this review, we intend to summarize the modes of regulated cell death other than apoptosis, and discuss their implications in toxicology. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. [Interest of toxicological analysis for poisonings].

    Science.gov (United States)

    Mégarbane, Bruno; Baud, Frédéric J

    2008-04-30

    The clinical approach of the poisoned patients is mainly based on the analysis of the circumstances of intoxication and the search for toxidromes. Toxicological analysis aims to detect the toxicants or measure their concentrations, in order to confirm the hypothesis of poisoning, to evaluate its severity and to help the follow-up regarding the treatment efficiency. Emergent toxicological analysis appears only useful if the method is specific and the results rapidly obtained. Therefore, systematic screening using immunochesmistry-based tests is not recommended in the situation of emergency. Measurement of blood concentrations of the toxicants is only indicated if it may influence the patient management. However, in the perspective of research, the study of toxicokinetic/toxicodynamic relationships, i.e. the relationships between the toxicant effects and its blood concentrations, may be helpful to understand the inter-individual variability of the response to a toxicant.

  12. Toxicology of Nanomaterials: Permanent interactive learning

    Directory of Open Access Journals (Sweden)

    Castranova Vince

    2009-10-01

    Full Text Available Abstract Particle and Fibre Toxicology wants to play a decisive role in a time where particle research is challenged and driven by the developments and applications of nanomaterials. This aim is not merely quantitative in publishing a given number of papers on nanomaterials, but also qualitatively since the field of nanotoxicology is rapidly emerging and benchmarks for good science are needed. Since then a number of things have happened that merit further analysis. The interactive learning issue is best shown by report and communications on the toxicology of multi-wall carbon nanotubes (CNT. A special workshop on the CNT has now been organized twice in Nagano (Japan and this editorial contains a summary of the most important outcomes. Finally, we take the opportunity discuss some recent reports from the nanotech literature, and more specifically a Chinese study that claims severe consequences of nanoparticle exposure.

  13. Pharmacological and toxicological evaluation of Urtica dioica.

    Science.gov (United States)

    Dar, Sabzar Ahmad; Ganai, Farooq Ahmad; Yousuf, Abdul Rehman; Balkhi, Masood-Ul-Hassan; Bhat, Towseef Mohsin; Sharma, Poonam

    2013-02-01

    Medicinal plants are a largely unexplored source of drug repository. Urtica dioica L. (Urticaceae) is used in traditional medicine to treat diverse conditions. The present study describes the antidiabetic, antiinflammatory, antibacterial activity, and toxicological studies of Urtica dioica. U. dioica leaves were subjected to solvent extraction with hexane, chloroform, ethyl acetate, methanol, and aqueous, respectively, and screened for antidiabetic (300 mg/kg bw by glucose tolerance test; GTT), antiinflammatory (200 mg/kg bw by rat paw edema assay) and antibacterial activities [by disc-diffusion and minimum inhibitory concentration (MIC) assays]. Toxicological studies were carried on Artemia salina and Wistar rats; phytochemical analyses were carried out, using chromatographic and spectroscopic techniques. The aqueous extract of U. dioica (AEUD) significantly (p 1000 μg/mL each on A. salina. Our results showed that the U. dioica leaves are an interesting source of bioactive compounds, justifying their use in folk medicine, to treat various diseases.

  14. Toxicology in Asia--Past, present, and future.

    Science.gov (United States)

    Satoh, T

    2015-12-01

    The Asian Society of Toxicology (ASIATOX), which consists of the seven national toxicology member societies of Japan, Korea, China, Taiwan, Thailand, Singapore, and Iran, now boasts of more than 3,000 members from a variety of industries, academia, and regulatory organizations. ASIATOX congresses are spaced three years apart and rotated among the member societies. In 1995, ASIATOX joined the International Union of Toxicology (IUTOX) as a regional society, and now serves as the scientific voice of toxicology in Asia under the IUTOX umbrella. Since its inauguration, the society has worked diligently to handle matters deemed essential to promoting the vision set fourth by its founders. Future perspectives of ASIATOX include the establishment of education and training programs, and the certification and accreditation of toxicologists. As the leading voice of toxicology in Asia, the society seeks to extend knowledge of toxicological issues to developing nations in Asia based on the following missions and goals: (1) to provide leadership as a worldwide scientific organization that objectively addresses global issues involving the toxicological sciences, (2) to broaden the geographical base of toxicology as a discipline and profession to all countries of the world, and (3) to pursue capacity building in toxicology, particularly in developing countries, while utilizing its global perspective and network to contribute to the enhancement of toxicology education and the career development of young toxicologists. © The Author(s) 2015.

  15. Toxicological evaluation of two novel bitter modifying flavour compounds: 3-(1-((3,5-dimethylisoxazol-4-ylmethyl-1H-pyrazol-4-yl-1-(3-hydroxybenzylimidazolidine-2,4-dione and 3-(1-((3,5-dimethylisoxazol-4-ylmethyl-1H-pyrazol-4-yl-1-(3-hydroxybenzyl-5,5-dimethylimidazolidine-2,4-dione

    Directory of Open Access Journals (Sweden)

    Donald S. Karanewsky

    Full Text Available A toxicological evaluation of two novel bitter modifying flavour compounds, 3-(1-((3,5-dimethylisoxazol-4-ylmethyl-1H-pyrazol-4-yl-1-(3-hydroxybenzylimidazolidine-2,4-dione (S6821, CAS 1119831-25-2 and 3-(1-((3,5-dimethylisoxazol-4-ylmethyl-1H-pyrazol-4-yl-1-(3-hydroxybenzyl-5,5-dimethylimidazolidine-2,4-dione (S7958, CAS 1217341-48-4, were completed for the purpose of assessing their safety for use in food and beverage applications. S6821 undergoes oxidative metabolism in vitro, and in rat pharmacokinetic studies both S6821 and S7958 are rapidly converted to the corresponding O-sulfate and O-glucuronide conjugates. S6821 was not found to be mutagenic or clastogenic in vitro, and did not induce micronuclei in bone marrow polychromatic erythrocytes in vivo. S7958, a close structural analog of S6821, was also found to be non-mutagenic in vitro. In short term and subchronic oral toxicity studies in rats, the no-observed-adverse-effect-level (NOAEL for both S7958 and S6821 was 100 mg/kg bw/day (highest dose tested when administered as a food ad-mix for either 28 or 90 consecutive days, respectively. Furthermore, S6821 demonstrated a lack of maternal toxicity, as well as adverse effects on fetal morphology at the highest dose tested, providing a NOAEL of 1000 mg/kg bw/day for both maternal toxicity and embryo/fetal development when administered orally during gestation to pregnant rats. Keywords: S6821, S7958, FEMA GRAS, Subchronic toxicological evaluation, Genetic toxicological evaluation

  16. Effect of inhaled formoterol and budesonide on exacerbations of asthma

    NARCIS (Netherlands)

    Pauwels, RA; Lofdahl, CG; Postma, DS; Tattersfield, AE; OByrne, P; Barnes, PJ; Ullman, A

    1997-01-01

    Background The role of long-acting, inhaled beta(2)-agonists in treating asthma is uncertain. In a double-blind study, we evaluated the effects of adding inhaled formoterol to both lower and higher doses of the inhaled glucocorticoid budesonide. Methods After a four-week run-in period of treatment

  17. Terbutaline accumulates in blood and urine following daily therapeutic inhalation

    DEFF Research Database (Denmark)

    Krogh, Nanna; Rzeppa, Sebastian; Dyreborg, Anders

    2017-01-01

    ×d) of inhaled terbutaline. After inhalation of terbutaline at each trial, subjects performed 90 min of bike ergometer exercise at 65% of maximal oxygen consumption after which they stayed inactive. Blood and urine samples were collected before and after inhalation of terbutaline. Samples were analyzed by high...

  18. Evaluation of Inhaler Techniques Among Asthma Patients Seen in ...

    African Journals Online (AJOL)

    hanumantp

    Drug inhalation is an important and a common mode of .... to evaluate the use of inhaler technique among asthma patients in a .... The median duration of the use of the inhalers is 24 ..... Scalabrini A, Cukier A. Incorrect application technique of.

  19. Teaching inhaler use in chronic obstructive pulmonary disease patients.

    Science.gov (United States)

    Lareau, Suzanne C; Hodder, Richard

    2012-02-01

    To review barriers to the successful use of inhalers in patients with chronic obstructive pulmonary disease (COPD), and the role of the nurse practitioner (NP) in facilitating optimum inhaler use. Review of the national and international scientific literature. Pharmacologic treatment of COPD patients comprises mainly inhaled medications. Incorrect use of inhalers is very common in these individuals. Some of the consequences of poor inhaler technique include reduced therapeutic dosing, medication adherence, and disease stability, which can lead to increased morbidity, decreased quality of life, and a high burden on the healthcare system. Knowledgeable evaluation and frequent reassessment of inhaler use coupled with education of patients, caregivers, and healthcare professionals can significantly improve the benefits COPD patients derive from inhaled therapy. Patient education is vital for correct use of inhalers and to ensure the effectiveness of inhaled medications. The NP has a critical role in assessing potential barriers to successful learning by the patient and improving inhaler technique and medication management. The NP can also facilitate success with inhaled medications by providing up-to-date inhaler education for other healthcare team members, who may then act as patient educators. ©2011 The Author(s) Journal compilation ©2011 American Academy of Nurse Practitioners.

  20. Knowledge of spacer device, peak flow meter and inhaler technique ...

    African Journals Online (AJOL)

    Background: Metered dose inhalers are cornerstone in effective management of bronchial asthma when correctly used. Most studies hitherto have focused on assessing patient's knowledge of inhaler technique. We sought to assess the knowledge of inhaler technique, spacer device and peak flow meter among doctors and ...